for educational and safety purposes
Every cognitive compound in the wiki; the racetams, cholinergics, ampakines, and neurotrophics people actually use for memory, focus, and clarity.
154 sourced · 276 reference
Dihexa is a small angiotensin IV analogue engineered at Washington State University to do something most peptides cannot, which is survive oral dosing and cross into the brain. Where most cognitive compounds nudge neurotransmitter levels, it was designed to act on the machinery that physically builds connections between neurons, and the preclinical reports are striking: reversed amnesia in animal models, restored spatial learning in Alzheimer's-model mice, and measurable growth of new synapses. The mechanism originally proposed for that effect, amplification of the HGF and c-Met growth-factor system, no longer rests on its original evidence; the central paper was retracted in 2025 after image manipulation was found, two supporting papers from the same laboratory were retracted alongside it, and the paper that first introduced Dihexa carries an expression of concern that is still in force. What the compound does is therefore an open question rather than a settled one. It has never been through a registered human trial, and the clinical programme built on the same mechanism, using an injectable modified version, missed its main Alzheimer's endpoint in 2024.
Semax is a synthetic peptide nootropic and neuroprotective agent based on a fragment of adrenocorticotropic hormone (ACTH), developed in Russia and used there clinically for cognition, stroke, and brain injury. It rapidly raises the brain's own growth factors, BDNF and NGF, and modulates dopamine and serotonin, underpinning its reputation for sharper focus, memory, and mental drive. Delivered as a nasal spray and stripped of any hormonal activity, it pairs cognitive support with genuine neuroprotection.
Selank is a synthetic peptide anxiolytic and nootropic derived from the immune peptide tuftsin, developed in Russia as a non-sedating, non-addictive alternative to conventional anti-anxiety drugs. It eases anxiety while supporting memory and attention, and animal research links these effects to modulation of GABA, serotonin, and brain-derived neurotrophic factor. Typically given as a nasal spray, it offers calm and cognitive support without the dependence or withdrawal associated with benzodiazepines.
Cerebrolysin is a neuropeptide preparation that mimics the brain's own neurotrophic factors to support neuronal protection, repair, and plasticity. Widely used across Europe and Asia for stroke, dementia, and traumatic brain injury, it is one of the most established neurotrophic therapies in clinical practice. For those focused on brain health and neuroregeneration, Cerebrolysin is a uniquely biologically active peptide preparation.
P21 (P021) is a small, orally active neurotrophic peptide mimetic derived from ciliary neurotrophic factor, engineered to deliver the brain-building benefits of a neurotrophic factor without the drawbacks that stalled earlier protein therapies. It enhances hippocampal neurogenesis and raises BDNF while lowering the tau-driving kinase GSK-3beta, and in Alzheimer's models it reduced tau pathology and rescued cognition and synaptic plasticity [1][2]. Its blood-brain-barrier permeability and clean design make it a genuinely exciting frontier compound for neuroprotection.
PE-22-28 is a fast-acting mood peptide with a genuinely clever mechanism, engineered from the natural antidepressant peptide spadin to be more potent and stable. It blocks the TREK-1 potassium channel that sits in mood circuits and dampens serotonin signaling, and animals bred without TREK-1 are naturally resistant to depression [2]. In rodent studies its shortened design achieved dramatically stronger TREK-1 inhibition than spadin, produced antidepressant-like effects within days, and boosted neurogenesis, making it one of the more exciting frontier tools in the mood space [1].
Adamax is a research peptide built from Semax by capping it with an adamantane group, a bulky lipophilic cage intended to improve stability and passage into the brain. No published study examines Adamax itself, so everything on this page about how it works is reasoned from the Semax literature rather than measured for this compound; the claim that it is more potent than its parent has never been tested. For readers who already know the Semax family, it is best understood as an untested modification of a well-documented peptide rather than an upgraded version of one.
Noopept is one of the most extensively researched dipeptide nootropics, a proline-containing compound designed as a peptide analog of piracetam with far greater potency by weight. Its standout quality is neuroprotection; in cellular models it guarded neurons against oxidative and amyloid-related damage more effectively than piracetam or classic antioxidants, while attenuating tau hyperphosphorylation [1][3]. Studied for memory restoration and neuroprotection, it also raises endogenous NGF and BDNF and activates adaptive stress-response pathways.
Phenylpiracetam (phenotropil, carphedon) is a phenylated derivative of piracetam, developed in Russia and used clinically as a nootropic, with reported effects on focus, physical endurance, and tolerance to cold and fatigue. The added phenyl group makes it considerably more potent than the parent racetam and confers a distinct mechanism, selective inhibition of the dopamine transporter, which is thought to underlie its stimulant-like, motivating properties. It was among the first cognitive enhancers prohibited in competitive sport, having been banned by anti-doping authorities in 1998.
Acetyl-L-carnitine (ALCAR), also known as levacecarnine, is the acetylated form of the amino-acid derivative L-carnitine. It occurs naturally in the body, where it participates in mitochondrial energy metabolism by helping transport fatty acids for breakdown and by supplying acetyl groups. Sold widely as a dietary supplement and used as a medicine in some countries, it has been studied for depression, nerve pain, and age-related cognitive decline.
Adrafinil (CRL-40028) is a prodrug of modafinil and one of the most accessible routes to clean, sustained wakefulness and focus. Once converted by the liver into modafinil, it delivers the same eugeroic, alertness-promoting effect that made modafinil famous, without requiring a prescription in many countries. Marketed originally in Europe as Olmifon, it remains a favorite among those seeking long-lasting, jitter-light energy and mental stamina.
Alpha-GPC (L-alpha glycerylphosphorylcholine) is a highly bioavailable choline source that readily crosses the blood-brain barrier to supply the raw material for acetylcholine, the neurotransmitter central to memory, focus, and muscular power. Clinical and meta-analytic evidence supports its use for cognitive performance, making it one of the most reliable cholinergic nootropics available [1][2]. It additionally potentiates growth hormone release and is widely used across both cognitive and athletic supplementation [4][5].
Aniracetam is a fat-soluble member of the racetam family and one of the original ampakines, a positive allosteric modulator of AMPA-type glutamate receptors used as a cognition enhancer. By slowing the desensitization of these excitatory receptors it strengthens the synaptic transmission tied to learning and memory, and it has been used clinically abroad for cognitive symptoms after stroke and in dementia. Its principal metabolite, 2-pyrrolidinone, has been reported to produce a longer-lasting enhancement of AMPA-receptor function through a CaMKII-dependent pathway. It is also noted for anxiolytic and mood effects in animal models.
Atomoxetine is a selective norepinephrine reuptake inhibitor used to treat attention deficit hyperactivity disorder (ADHD) in children, adolescents, and adults. Unlike stimulant ADHD medications, it is not a controlled substance and carries essentially no potential for misuse, since it does not produce euphoria. Developed by Eli Lilly and approved in the United States in 2002 under the brand name Strattera, it works by blocking the norepinephrine transporter and is usually considered a second-line option after stimulants.
Bacopa monnieri is a creeping wetland herb of the family Plantaginaceae, known in Ayurvedic tradition as brahmi and used for centuries as a remedy for memory and mental clarity. Its characteristic compounds are a group of triterpenoid saponins called bacosides, and standardized extracts are marketed as dietary supplements aimed at cognition. Clinical trials suggest it may modestly aid memory in some settings, though the overall evidence is mixed and it is not an approved medicine.
Caffeine is a central nervous system stimulant of the methylxanthine class and the most widely consumed psychoactive substance in the world. A purine alkaloid found naturally in coffee beans, tea leaves, cacao, and other plants, it is used to restore alertness, reduce fatigue, and sharpen concentration. It is legal and largely unregulated in most countries, and it also has established medical uses, including the treatment of apnea in premature infants.
Cerebramin is an oral extract of animal brain tissue sold in Russia as a food supplement for memory and mental stamina, and the claims made for it rest on Russian language reports rather than on controlled trials anyone else has replicated.
Cerluten is a capsule of peptide fractions extracted from the brain tissue of young cattle, sold as a supplement for the central nervous system; it is an organ extract and not a defined peptide.
Choline is an essential nutrient that the body needs for building cell membranes, making the neurotransmitter acetylcholine, and supplying methyl groups used in metabolism [1][2]. Chemically it is a small water-soluble molecule, a quaternary ammonium compound, found in foods such as eggs, liver, meat, fish, and soybeans [1][2]. The body can make a little choline in the liver, but most people must obtain it from the diet, and it was formally recognized as an essential nutrient in 1998 [1][2]. Adequate choline is especially important during pregnancy for fetal brain development [3].
Coluracetam has the most distinctive proposed mechanism in the racetam family. Rather than acting at a receptor, it was designed to raise the rate at which neurons take up choline, the raw material the brain uses to build acetylcholine. Mitsubishi developed it in Japan in the 1990s as an Alzheimer's candidate, and it was later carried into depression research and through a completed 115-person trial. Readers who use it describe sharper focus and, unusually for a nootropic, changes in visual vividness. The evidence for the mechanism is narrower than the reputation: the choline-uptake effect was shown in animals whose cholinergic neurons had been deliberately lesioned first and not in normal tissue, and an independent group at Pfizer testing the same transporter across four separate methods found no effect at all. That lesion-dependence is itself worth understanding, because it would predict a quieter effect in a healthy brain rather than none. No human trial has yet reported a cognitive result; the 2009 study completed without publishing its outcomes.
Cortexin is a polypeptide preparation made from the cerebral cortex of cattle, consisting of a mixture of low-molecular-weight peptides, amino acids, and trace elements. Marketed as a neuroprotective and nootropic medicine, it is registered and prescribed mainly in Russia and other post-Soviet countries, where it is given by intramuscular injection for stroke recovery, cognitive disorders, and other neurological conditions. It is not approved by Western drug regulators, and most clinical evidence for it comes from Russian-language literature.
Creatine is a nitrogen-containing organic acid that occurs naturally in vertebrates, where it helps recycle the cellular energy carrier adenosine triphosphate (ATP), chiefly in muscle and brain. The body makes it in the liver, kidneys, and pancreas from the amino acids arginine, glycine, and methionine, and it is also obtained from animal foods such as meat and fish. First isolated from meat by the French chemist Michel Eugene Chevreul in 1832, creatine is today one of the most widely studied and used dietary supplements, valued mainly for improving strength and high-intensity exercise performance.
DNSP-11 is a synthetic 11-amino-acid peptide copied from the pro-region of GDNF, a natural protein that helps dopamine-producing brain cells survive. In rats and in a small group of monkeys it raised dopamine activity and protected dopamine neurons against chemical damage, which is why it is discussed as a possible Parkinson's disease treatment. The evidence is entirely animal and cell-culture work, almost all of it from a single laboratory at the University of Kentucky; no person has ever received it in a registered clinical trial, and the receptor it acts on has never been identified. Material sold online under this name is an unapproved research chemical with no human safety data behind it.
EPObis is a synthetic dendrimeric peptide designed from the binding Site 1 sequence of human erythropoietin, guided by the crystal structure of the erythropoietin-receptor complex. It binds the erythropoietin receptor and reproduces the cytokine's tissue-protective signaling; in cultured neurons it promotes neurite outgrowth and survival in a receptor-dependent manner. Unlike erythropoietin itself, EPObis is non-erythropoietic, so it activates protective pathways without stimulating red blood cell production, and after systemic administration it crosses the blood-brain barrier into the cerebrospinal fluid. In rodent studies it reduces tumor necrosis factor release from activated macrophages and microglia, delays clinical signs in experimental autoimmune encephalomyelitis, and enhances working memory, marking it as an experimental neuroprotective and anti-inflammatory research peptide.
Fladrafinil (CRL-40,941) is a synthetic wakefulness drug from the same French research programme of the 1970s and 1980s that produced modafinil and adrafinil; chemically it is adrafinil with a fluorine atom added to each of its two rings. It was never approved or marketed as a medicine anywhere, and it now circulates online as a research chemical and turns up in products sold as nootropic supplements. The body converts it into flmodafinil, which is what actually produces the effect; that conversion has been demonstrated directly in people, but almost nothing else about the drug has been tested in humans. There are no efficacy trials, no safety studies and no published measurement of what it binds to, so claims that it sharpens focus or that it is several times stronger than adrafinil rest on marketing and a 1984 patent rather than on evidence.
Flmodafinil, also written FL-Modafinil and originally coded CRL-40,940, is a fluorinated analogue of modafinil in which both phenyl rings carry a fluorine. It is a genuinely different molecule from modafinil and not a brand of it, which is worth stating plainly because the two names are routinely sold as though interchangeable. Fladrafinil (CRL-40,941) is its prodrug, standing to flmodafinil roughly as adrafinil stands to modafinil. Vendors commonly claim greater potency and better solubility than modafinil; those claims come from early rodent work and from sellers rather than from human trials.
Galantamine is a plant-derived alkaloid, isolated from snowdrops and related plants of the Amaryllidaceae family, used to treat the memory and thinking difficulties of mild-to-moderate Alzheimer's disease. It has an unusual dual action on the cholinergic system: it inhibits the enzyme acetylcholinesterase, and it separately acts as an allosteric potentiating ligand that binds a site distinct from the neurotransmitter's on nicotinic acetylcholine receptors, making them respond more strongly to acetylcholine. Marketed under names such as Razadyne and Reminyl, it has also been studied as a nerve-agent countermeasure and, more curiously, as an aid to lucid dreaming.
Glycine is the smallest amino acid; the body makes it from serine and it is also eaten in food, most densely in gelatin and collagen. It does two opposite jobs in the nervous system: it opens inhibitory chloride channels in the spinal cord and brainstem, and it is also the required partner molecule that the excitatory NMDA receptor must have bound before glutamate can open it. Supplement interest centres on sleep and on schizophrenia; the sleep evidence is thin and comes largely from small studies run by an amino acid manufacturer, while the schizophrenia evidence is genuinely mixed, because early positive trials at very large doses were not confirmed by the larger CONSIST trial. Glycine is cheap and well tolerated, but the honest reading is that the reported effects are modest and have not replicated consistently.
Huperzine A is a naturally occurring alkaloid isolated from the Chinese club moss Huperzia serrata, a plant long used in traditional Chinese medicine. It is a potent, selective, and long-acting reversible inhibitor of acetylcholinesterase, and it additionally acts as a non-competitive antagonist of the NMDA glutamate receptor at one of the polyamine binding sites, a combination that has made it of interest for memory, dementia, and neuroprotection. In China it is used as an approved drug, whereas in the United States it is sold as a dietary supplement.
L-Tyrosine is an aromatic amino acid used to build proteins and to make several important signaling molecules. Because the body can produce it from the essential amino acid phenylalanine, it is usually classed as non-essential, or conditionally essential when phenylalanine is scarce. It is the raw material for the catecholamine neurotransmitters dopamine, norepinephrine, and epinephrine, as well as for thyroid hormones and the pigment melanin, and it is sold as a supplement studied mainly for mental performance under stress.
Lemairamin, sold as WGX-50 or gx-50, is a small molecule found naturally in Sichuan pepper (Zanthoxylum bungeanum and related species); chemically it is a simple cinnamamide, not an alkaloid and not a stimulant. Laboratory work suggests it switches on the alpha-7 nicotinic acetylcholine receptor, quiets inflammatory activity in the immune cells of the brain and gut, and can break apart the amyloid clumps associated with Alzheimer's disease. Every one of those findings comes from cells, worms, zebrafish, rats or mice; no person has been given this compound in any published study, and no clinical trial of it has ever been registered. The honest position is that WGX-50 is an interesting preclinical candidate with no evidence whatsoever that it does anything in humans.
Magnesium L-threonate is a magnesium salt of L-threonic acid, a sugar acid derived from vitamin C. It was developed as a supplemental form intended to raise magnesium levels in the central nervous system more effectively than conventional magnesium salts; unlike most oral forms, it has been shown to increase magnesium in the cerebrospinal fluid and within neurons, where it up-regulates NR2B-containing NMDA receptors and increases the density of functional synapses. In animal studies these actions are associated with improved learning and enhanced retention of fear extinction, and it is studied mainly for possible effects on memory, cognition, sleep, and anxiety. First described in a 2010 laboratory study, it is sold commercially under names such as Magtein.
Magnesium N-Acetyl Taurinate is a magnesium salt where the mineral is paired with N-acetyltaurine, which is an acetylated (chemically capped) version of the amino acid taurine. The pitch behind it is delivery; the makers claim it is a more membrane-friendly form (one they say slips across cell membranes more easily) meant to carry both magnesium and its taurine partner across the blood-brain barrier (the tight filter that guards the brain) and into the central nervous system. Once inside, magnesium does its usual double job; it sits in the NMDA glutamate receptor like a natural gatekeeper that keeps that excitatory channel from firing too easily, and it works as a cofactor (helper molecule) for hundreds of enzymes. The taurine that is thought to be freed after the acetyl cap is cleaved (a release step that is not well characterized in people) is a calming neuromodulator (a molecule that gently tunes nerve signaling) that nudges GABA-A and glycine receptors and helps keep cellular calcium and water balance in check. People reach for it for stress, relaxation, sleep, and general cognitive support. Straight talk here; this is a newer, branded form and the human clinical evidence is early and thin, so most of the story is still mechanistic or preclinical rather than proven in large human trials.
Memantine (brand names Namenda and Ebixa) is an NMDA receptor antagonist approved for moderate to severe Alzheimer's disease; it calms excess glutamate signaling to protect neurons while leaving the normal signaling needed for memory and learning intact [1][2]. What makes it unusual is its voltage-dependent, fast-off-rate binding; it blocks the constant, low-level 'noise' of glutamate but steps aside when a real learning signal arrives, so it doesn't cloud cognition the way stronger blockers (like ketamine) do. It is also more than a pure NMDA blocker; at or near therapeutic brain concentrations it reaches a spread of remote targets, agonizing the high-affinity state of the dopamine D2 receptor, antagonizing 5-HT3 serotonin receptors and several nicotinic acetylcholine receptors (alpha-7, alpha-4/beta-2, alpha-3/beta-4 and alpha-9/alpha-10), and weakly engaging sigma-1 receptors; see the affinity table below for the full fingerprint. Beyond Alzheimer's it is being investigated for a range of conditions; it shows the most promise for the negative symptoms of schizophrenia (social withdrawal, apathy, blunted motivation) and as a mood stabilizer in bipolar disorder, with earlier signals in ADHD (often as an adjunct to a stimulant), anxiety and OCD, and autism.
Modafiendz is a fluorinated, N-methylated analog of the wakefulness agent modafinil, marketed online as a next-generation nootropic alternative. It is built around the same eugeroic blueprint that made modafinil a favorite for focus and sustained alertness, with structural tweaks intended to modify its activity. Because the analog itself has not been formally studied, it is best understood as an experimental research chemical riding on the well-mapped pharmacology of its parent.
N-PEP-12 is an oral dietary supplement of small brain-derived peptides and free amino acids, sold as Memoprove and described by its own investigators as a lower-potency, needle-free relative of the injectable neurotrophic drug Cerebrolysin. Small, mostly manufacturer-linked studies report modest short-term gains in memory and brain EEG activity in aging adults and in stroke recovery. It is an appealing, gentle nootropic idea, but the human evidence is thin and largely industry-linked, and the core assumption that oral brain peptides survive digestion to reach the brain remains pharmacologically unproven.
Nemifitide (originally coded INN 00835, and briefly called netamiftide) is a synthetic pentapeptide that was developed as an injectable antidepressant. Its sequence is 4-fluoro-L-phenylalanyl-trans-4-hydroxy-L-prolyl-L-arginyl-glycyl-L-tryptophanamide, and it is a structural analog of MIF-1 (melanocyte-inhibiting factor-1, the tripeptide Pro-Leu-Gly-NH2). It was studied by Innapharma, later Tetragenex Pharmaceuticals, and reached Phase II trials in major depressive disorder before development stalled; it was never approved. The interesting thing about it is the mismatch between its pharmacokinetics and its effect: the peptide clears the blood in well under an hour, yet the antidepressant response reported in trials came on within days and lasted weeks to months after a short dosing course. It was given as a subcutaneous injection, not a pill, and its tolerability was consistently good with side effects limited mostly to the injection site.
Oxiracetam is a synthetic compound from the racetam family and a close chemical relative of piracetam; it was developed in Italy in the 1980s as a prescription drug for memory and attention problems in dementia. Older European trials in dementia patients generally reported small improvements on cognitive test scores, but the modern evidence is split: a 590-patient Chinese trial in traumatic brain injury found a real benefit, while a 500-patient Korean trial found none for preventing cognitive decline after stroke, and South Korea then withdrew the drug. Nobody has established how it works; a standard 19-target receptor screen found no measurable binding at concentrations up to 30 micromolar, and no binding constant for oxiracetam at any brain receptor exists in the published literature. It remains in clinical use in China and is sold elsewhere as an unapproved powder, with a mild side-effect record but no trial evidence at all that it improves cognition in healthy people.
Paraxanthine is what caffeine mostly becomes. Around 70 to 80 percent of a caffeine dose is converted by the liver enzyme CYP1A2 into paraxanthine, so for most of the time a coffee is working, the compound doing the work is this one [14]. Selling it directly is an attempt to skip a step that varies enormously between people: CYP1A2 activity differs several-fold across individuals, which is a large part of why the same espresso is pleasant for one person and unpleasant for another. Human trials are small but real, and they point at improved cognition at modest doses with less of the sleep disruption caffeine causes [4][6]. It is the most credible caffeine alternative on this site, and the evidence base behind it is still thin and largely tied to the company selling it.
Phenylalanine is an essential amino acid and the first step in making dopamine and noradrenaline: the body converts it to tyrosine, tyrosine to L-DOPA, and L-DOPA to dopamine. That chain is the entire basis for taking it, and it is also the reason to be measured about it, because supplying more of the first ingredient does not reliably speed up a pathway that is regulated further downstream. The best-supported use is not mood at all; L-phenylalanine combined with light therapy has a real if modest evidence base in vitiligo [9][10]. The critical safety fact is short and absolute: anyone with phenylketonuria must not take it [7].
Pyrroloquinoline quinone (PQQ) is a small quinone compound that acts as a redox cofactor and antioxidant. First described in bacteria, where it serves as a cofactor for certain enzymes, it also occurs in trace amounts in many foods and in human tissues. It was proposed to be a new mammalian vitamin, a claim that remains debated, although dietary deprivation has been reported to impair growth, reproduction, and immune function in animals; it is also noted for stimulating mitochondrial biogenesis through PGC-1-alpha and for promoting nerve growth factor synthesis. It is sold as a dietary supplement and studied for effects on mitochondrial function and cognition, though it is not classed as an essential vitamin for humans.
Pregabalin (Lyrica) is a widely prescribed gabapentinoid that delivers fast, reliable relief from anxiety and nerve pain by calming overexcited neurons [1][3]. It binds the alpha-2-delta subunit of voltage-gated calcium channels, dialing down the release of excitatory neurotransmitters, a targeted mechanism that underlies its approved uses in generalized anxiety disorder, neuropathic pain, fibromyalgia, and epilepsy [1][6]. Valued for its rapid onset and predictable, linear pharmacokinetics, pregabalin is one of the most established calming agents in modern neurology and psychiatry [3][6].
Pregnenolone (3β-hydroxypregn-5-en-20-one) is an endogenous neurosteroid and the first steroid synthesized from cholesterol, making it the obligatory precursor of every other steroid hormone, including progesterone, dehydroepiandrosterone (DHEA), cortisol, the sex steroids, and the neuroactive metabolites allopregnanolone and pregnenolone sulfate. Once regarded as a metabolically inert intermediate, it is now recognized as a signaling molecule in its own right, most notably as an endogenous negative allosteric modulator of the type-1 cannabinoid receptor (CB1, the principal brain receptor for THC) and as a ligand for microtubule-associated protein 2 (MAP2, a neuronal cytoskeletal scaffolding protein), through which it promotes microtubule assembly and neurite outgrowth. Synthesized de novo in the brain by neurons and glia, it is investigated as an adjunctive treatment for schizophrenia, mood disorders, and cannabis-related conditions, and is sold over the counter as a nootropic and hormonal supplement.
Pterostilbene is a naturally occurring stilbenoid closely related to resveratrol, from which it differs by carrying two methoxy groups in place of hydroxyl groups. It is found chiefly in blueberries, grapes, and the heartwood of certain trees, where it serves as a defensive phytoalexin. The methoxy substitution makes it substantially more lipophilic, metabolically stable, and blood-brain-barrier permeable than resveratrol; in Alzheimer's-model mice it improved cognition and reduced neuroinflammation at dietary doses that were ineffective for resveratrol, apparently acting through PPAR-alpha rather than the sirtuins. It has been studied in humans in combination with nicotinamide riboside to raise NAD+ levels, and is sold as a dietary supplement rather than an approved medicine.
Oroxylin A is a plant flavonoid from the bark of the Indian trumpet tree (Oroxylum indicum) and from Chinese skullcap; consumers almost never buy the pure compound, they buy Sabroxy, a standardised bark extract in which oroxylin A is one of three flavonoids. It is marketed for memory and focus, and the animal work points to two mechanisms: it blocks the benzodiazepine site on the GABA-A receptor, releasing the brain's main braking signal, and it slows dopamine reuptake in roughly the way ADHD stimulants do. Human evidence is thin and rests on a single 12-week trial in 82 older adults with memory complaints; that trial was paid for by the ingredient's manufacturer, had a company founder as a co-author, found gains on some memory tasks but not most other measures, and applied no statistical correction for testing many outcomes at once. A separate Phase I study showed pure oroxylin A is tolerated up to 2400 mg in healthy volunteers, but no trial has ever shown the pure compound improves cognition in people.
Sarcosine, or N-methylglycine, is a non-proteinogenic amino acid and a natural intermediate in the metabolism of glycine and choline. In pharmacology it is best known as an inhibitor of the type 1 glycine transporter (GlyT1), a property that has made it a candidate add-on therapy for schizophrenia through enhancement of NMDA-receptor signaling. It has separately drawn attention as a metabolite whose levels have been linked, though not without debate, to prostate cancer progression.
Sulbutiamine is a synthetic derivative of thiamine, or vitamin B1, formed by joining two modified thiamine molecules into a fat-soluble disulfide. This lipophilic structure lets it cross the blood-brain barrier and raise thiamine levels in the brain more readily than thiamine itself, which distinguishes it from benfotiamine, a related derivative that raises thiamine chiefly in peripheral tissues. Developed in Japan and marketed under names such as Arcalion, it is used to treat asthenia, a state of persistent weakness and fatigue, and is also taken off-label as a nootropic; more recent work implicates its disulfide group in cellular thiol-redox regulation.
Taltirelin (TA-0910, brand name Ceredist) is a synthetic, metabolically stable analog of thyrotropin-releasing hormone (TRH), the three-residue hypothalamic peptide. It was developed by Tanabe Seiyaku and approved in Japan in 2000 for spinocerebellar degeneration, where it is taken orally to help with ataxia and related symptoms. The interesting thing about taltirelin is that it was engineered to keep the central nervous system effects of TRH while shedding most of the hormonal ones; it is roughly 10 to 100 times more potent than native TRH at driving CNS arousal, yet its effect on thyroid hormone release is much weaker. It also lasts far longer in the body because it resists the enzymes that chew up natural TRH within minutes. Outside its approved use it gets discussed in nootropic and biohacker circles as a wakefulness-promoting, pro-cholinergic "analeptic" and neuroprotective agent, and there is a real preclinical literature behind those claims (Parkinson's models, ischemia, pain, respiratory stimulation). Human data outside spinocerebellar degeneration is thin, so most of what you read about it as a cognitive enhancer is extrapolation from animal work.
Vinpocetine is a semisynthetic compound derived from vincamine, an alkaloid found in the lesser periwinkle plant (Vinca minor). It has been used for more than three decades in parts of Europe and Asia as a prescription drug for cerebrovascular disorders such as stroke and dementia, and it is also sold as a dietary supplement marketed to support memory and cognition. Its regulatory status varies widely, and the clinical evidence for its benefits is limited.
Nefiracetam is a fat-soluble pyrrolidinone racetam that modulates cholinergic, glutamatergic, and calcium signaling. It potentiates neuronal nicotinic acetylcholine receptor currents at sub-nanomolar concentrations and enhances NMDA-receptor function and long-term potentiation through protein kinase C and CaMKII, giving it a pronounced pro-cognitive and neuroprotective profile in preclinical research; it has also been reported to reverse signaling deficits in a laboratory model of Rett syndrome. It has been studied for memory impairment, dementia, and post-stroke apathy and depression.
Fasoracetam is a racetam-class nootropic that acts on the glutamatergic and GABAergic systems; with repeated administration it up-regulates GABA-B and metabotropic glutamate (mGluR) receptors. It is one of relatively few racetams to have reached controlled human trials, having been evaluated in adolescents with attention-deficit hyperactivity disorder who carry variants in genes governing mGluR signaling. It remains an investigational compound and is not an approved medicine.
Piracetam is the original nootropic, the very compound for which the word 'nootropic' was coined, developed by Corneliu Giurgea in the late 1960s to enhance learning and memory [1]. A cyclic derivative of the neurotransmitter GABA, it has become the foundational template of the entire racetam family and remains one of the most widely studied cognitive enhancers in the world [1][4]. Prized for a remarkable safety record and effects that are most pronounced when brain function is impaired, piracetam supports memory, learning, and cerebral circulation, and is used clinically for cognitive decline, myoclonus, and stroke recovery [2][4][5].
TAK-653, also called osavampator or NBI-1065845, is an experimental oral drug that makes the brain's main excitatory receptor, the AMPA glutamate receptor, respond more strongly to glutamate the brain is already releasing; crucially it cannot switch the receptor on by itself, a design choice intended to avoid the seizure risk that stopped earlier drugs of this type. It is being developed as a fast-acting antidepressant for people whose depression has not responded to standard antidepressants. A 183-person Phase 2 trial found that 1 mg once daily beat placebo on a standard depression rating scale while 3 mg did not reach statistical significance, and five Phase 3 trials are now enrolling; those Phase 2 results have not yet been published in a peer-reviewed journal. It is approved nowhere in the world, it is not a legal supplement, and the entire published literature amounts to about ten papers, most of them written by employees of the companies that own it.
Modafinil is a prescription wakefulness-promoting drug, approved in the United States in 1998 for excessive sleepiness caused by narcolepsy, obstructive sleep apnea, and shift work disorder. It works mainly by blocking the dopamine transporter, the protein that clears dopamine out of the synapse; human brain imaging confirms it occupies roughly half of those transporters at ordinary doses, although it binds them far more weakly than classic stimulants do. The evidence that it reduces sleepiness in the three approved sleep disorders is strong and rests on large placebo-controlled trials, but the evidence that it improves thinking in healthy, well-rested people is much weaker; the best meta-analysis found only a small overall effect confined to one narrow memory task. It is a Schedule IV controlled substance in the United States, banned in competition by WADA, and carries warnings for rare but serious skin reactions and for making hormonal birth control less reliable.
Armodafinil is the prescription wakefulness drug sold as Nuvigil; it is one of the two mirror-image halves of modafinil, the longer-lasting half, so it does much the same job at a somewhat lower dose. In the United States it is approved only to reduce excessive sleepiness in adults with narcolepsy, obstructive sleep apnea, or shift work disorder, and the evidence for those three uses is genuinely solid; several 12-week placebo-controlled trials show people stay awake longer, though the benefit is measured in a few extra minutes of resisting sleep rather than a cure. Its one well-supported molecular action is weak blockade of the dopamine transporter, which brain scans confirm happens at ordinary doses; the histamine and orexin explanations that circulate online come from studies of modafinil, not of armodafinil itself. Outside the sleep indications the record thins out fast and is often negative, including a clean phase 3 failure for cancer-related fatigue, and this is a Schedule IV controlled drug carrying a pregnancy registry signal for birth defects.
CE-123 is a next-generation, thiazole-based modafinil analogue engineered for selective dopamine transporter inhibition and cognitive enhancement. In preclinical studies it sharpens memory and cognitive flexibility while crossing into the brain far more effectively than modafinil, and with less impulsivity. For research focused on motivation, focus, and cognition, CE-123 is a standout modern nootropic candidate.
Bromantane is an adamantane-derived actoprotector that delivers clean, non-jittery energy by increasing the body's own dopamine synthesis rather than forcing a release. Prized for boosting physical and mental stamina while carrying a genuine anti-anxiety quality, it stands out as a rare stimulant that builds resilience without a crash or dependence. For those seeking durable drive and stress resistance, bromantane is a uniquely compelling choice.
9-Me-BC is a small synthetic molecule from the beta-carboline family, chemically close to compounds that occur naturally in coffee, cooked meat and tobacco smoke; it is sold online as a nootropic and has never been approved as a medicine anywhere. In cell cultures and in rodents it raises dopamine levels, protects and partly regrows dopamine-producing neurons, and improved maze learning in rats, which is why it was proposed as a possible Parkinson's disease drug. The evidence is entirely preclinical; there is no human trial, no human dosing study and no human safety data at all, and almost every positive finding comes from a single research group in Germany. Two specific concerns remain unresolved: it inhibits the enzyme MAO-A at low concentrations, the same mechanism that makes prescription MAOI antidepressants risky with certain foods and drugs, and enzymes in the brain can convert it into a closely related molecule that is itself an established nerve toxin.
PPAP is a laboratory compound derived from selegiline that was designed to stimulate the brain without the uncontrolled neurotransmitter dumping that amphetamines cause. In rats it increases the dopamine and noradrenaline released when a nerve cell actually fires, an effect its developers named a catecholaminergic activity enhancer effect; unlike selegiline it does not block the enzyme MAO-B. A 2026 screening study also found it blocks dopamine reuptake, slightly more strongly than amphetamine did in the same assay. Almost the entire evidence base is rat and cell work from one Hungarian laboratory; PPAP has never been given to a human in any published study, so no human dose or safety information exists, and it has since appeared as an unregulated substance on the European drug market.
BPAP is an experimental laboratory compound created in the late 1990s by the Hungarian and Japanese team behind selegiline; it has never been approved as a medicine in any country. It is described as a "monoaminergic activity enhancer", meaning that in animal tissue it makes dopamine, noradrenaline and serotonin neurons release more transmitter when they fire, rather than forcing transmitter out the way amphetamine does; at higher concentrations it also blocks dopamine and noradrenaline reuptake. Essentially all the evidence comes from rats, mice and cell cultures, and almost all of it was produced by the two groups with a stake in the compound, namely Knoll's Semmelweis University laboratory and Fujimoto Pharmaceutical Corporation. No clinical trial in humans has ever been run or even registered, so claims about memory, mood, longevity or anti-aging benefit in people rest on no human evidence at all.
CDP-choline (citicoline, cytidine diphosphate-choline) is a naturally occurring compound that the body uses as an intermediate in making phosphatidylcholine, a major building block of cell membranes. Taken as a drug or dietary supplement, it supplies choline and cytidine to the brain and is studied for cognition, stroke recovery, and certain eye conditions. It is sold as a prescription medicine in some countries and as an over-the-counter supplement in others.
Donepezil is a medication used to treat the symptoms of dementia in Alzheimer's disease. It belongs to a class of drugs called cholinesterase inhibitors, which work by boosting levels of the signaling chemical acetylcholine in the brain. Developed by the Japanese company Eisai and approved in the United States in 1996 under the brand name Aricept, it is one of the most widely prescribed treatments for Alzheimer's dementia. Donepezil eases symptoms modestly but does not stop or reverse the underlying disease.
PRL-8-53 is a classic research nootropic famous for a single striking human study in which low oral doses significantly improved the retention of newly learned verbal information [1]. Chemically a methyl benzoate compound developed in the 1970s, it was reported to sharpen memory while potentiating the brain's dopaminergic and stimulant signaling [1][2]. Its reputation rests almost entirely on that early double-blind trial, as PRL-8-53 has never been independently replicated or brought to market, and it remains an obscure but intriguing research chemical [1][2].
Methylene Blue is a century-old phenothiazine compound that has been reinvented as one of the most intriguing metabolic and cognitive agents in modern research. At low concentrations it functions as a mitochondrial electron cycler, boosting cellular energy production while acting as an antioxidant, effects that underpin growing interest in brain performance and neuroprotection. Backed by an FDA-recognized clinical heritage in emergency medicine, it occupies a rare position bridging established pharmacology and frontier nootropic science.
NSI-189 is a first-in-class neurogenic compound built on a genuinely novel premise; rather than manipulating monoamines like conventional antidepressants, it stimulates the birth of new neurons in the hippocampus. This small, orally active molecule promotes neurogenesis of human hippocampus-derived neural stem cells and, in clinical testing for major depressive disorder, produced encouraging antidepressant and pro-cognitive signals [1][3]. Its dual mood and cognition profile makes it one of the more distinctive investigational compounds in the space.
J147 is an experimental neuroprotective compound that grew out of a curcumin-like scaffold, designed at the Salk Institute through phenotypic screens that mimic the aging brain rather than any single Alzheimer's protein. In mice it is potent, orally active, and brain-penetrant: it enhances memory, raises the neurotrophic factors BDNF and NGF, and can rescue cognition even when given late, after pathology is already advanced. Its molecular target was a mystery for years until 2018, when it was identified as the mitochondrial ATP synthase; gently modulating that enzyme flips on the AMPK/mTOR longevity pathway, tying Alzheimer's and ordinary brain aging to a shared mechanism. Crucially, essentially all of this is preclinical; a phase 1 safety study was reportedly initiated but no human efficacy results have been published. Treat J147 as a promising research compound, not a proven drug.
BPN14770, also known as zatolmilast, is an investigational drug that inhibits the phosphodiesterase-4D (PDE4D) enzyme through an allosteric mechanism, binding a regulatory domain rather than the catalytic site so that inhibition is only partial. This partial, subtype-selective action raises the signaling molecule cyclic AMP in the brain to enhance memory while avoiding the nausea and emesis that limited earlier pan-PDE4 inhibitors. It has been studied for Fragile X syndrome, where it improved cognition in a phase 2 trial, and for Alzheimer's disease; it reached phase 2 trials but is not approved for medical use.
ISRIB is an experimental laboratory compound that switches off a cellular alarm system called the integrated stress response; that alarm normally slows a cell's protein production when the cell is under strain. It works by clamping a protein machine called eIF2B into its active shape, which lets brain cells resume making the new proteins that forming a memory depends on. In mice and rats it speeds learning, restores memory weeks after a head injury, and reverses some age-related memory loss, at doses well under a milligram per kilogram. All of that evidence comes from cells and rodents; ISRIB has never been given to a person in a registered clinical trial, so there is no human dose, no human safety record, and no evidence it does anything in people.
Tropisetron is a prescription anti-nausea drug that blocks the serotonin 5-HT3 receptor, and it is used to stop the vomiting caused by chemotherapy or by surgery; it has been sold for that purpose since 1992 in Europe, Japan, Australia and much of Asia, but it was never approved in the United States. What sets it apart from the other drugs in its class is that it also binds tightly to a brain receptor called the alpha-7 nicotinic acetylcholine receptor, which is why researchers have tested it for fibromyalgia pain, for thinking problems in schizophrenia, and in animal models of Alzheimer's and Huntington's disease. The anti-nausea use is solidly established; every other use rests on small short trials, mostly fewer than 45 people and under two weeks long, or on animal work, and no regulator anywhere has approved it for any of them. Anyone reading the older literature should also know that a large slice of the post-surgical anti-nausea evidence base was fabricated and later retracted, so individual old trials in that area carry very little weight on their own.
SANA, also identified as MVD-1, is an orally active, non-stimulant thermogenic being explored for obesity and metabolic disease. As a salicylate-derived small molecule, it is designed to switch on creatine-dependent thermogenesis in fat cells, driving a futile creatine cycle that raises energy expenditure and releases energy as heat rather than blunting appetite. This mechanism-first approach, aimed at reducing body fat and liver fat while improving glucose control and preserving lean mass, represents one of the more novel ideas in the metabolic pipeline.
Selegiline, also known as L-deprenyl, is a selective and irreversible inhibitor of monoamine oxidase B (MAO-B), used in the treatment of Parkinson's disease and, in a transdermal patch form, of major depressive disorder. At low doses it selectively spares MAO-A, which avoids the dietary tyramine restrictions required by older monoamine oxidase inhibitors, though this selectivity is lost at higher doses. It is marketed under names including Eldepryl, Zelapar, and, as a skin patch, Emsam.
Agomelatine is a first-in-class antidepressant that acts through a mechanism unlike conventional agents, combining agonism at the melatonin MT1 and MT2 receptors with antagonism of the serotonin 5-HT2C receptor. This dual action resynchronizes disrupted circadian rhythms and increases dopamine and noradrenaline in the frontal cortex, and it is the only marketed antidepressant to work through the melatonergic system rather than monoamine reuptake. Approved in Europe as Valdoxan, it is noted for a relatively favorable tolerability profile, with fewer sexual side effects and less weight gain than SSRIs, though it requires monitoring of liver enzymes because of a risk of hepatotoxicity.
Picamilon (N-nicotinoyl-GABA, pikamilon) is a Soviet-developed nootropic that fuses niacin with the calming neurotransmitter GABA into a single molecule, engineered to carry GABA across the blood-brain barrier that GABA alone cannot cross [4]. Introduced in Russia as a cerebrovascular agent, it is prized for combining gentle, non-sedating relaxation with improved blood flow to the brain [2][3]. Once inside the brain it is thought to split back into niacin, a vasodilator, and GABA, which quiets neural overactivity, an elegant two-in-one design that made it a mainstay of Russian neurology [2][4].
Nimodipine is a dihydropyridine calcium channel blocker developed mainly to act on the blood vessels of the brain rather than as a general antihypertensive. Its principal approved role is preventing the delayed cerebral ischemia that can follow aneurysmal subarachnoid hemorrhage, a form of bleeding around the brain. It was patented in 1971 and reached clinical use in the 1980s, gaining United States approval in 1988. Because it relaxes cerebral arteries and shows relative selectivity for that circulation, it remains the only medication specifically approved to improve neurological outcomes after this type of stroke.
Tesofensine is a triple monoamine reuptake inhibitor, originally investigated for Parkinson's and Alzheimer's disease, that produced some of the largest weight losses reported for an appetite-suppressing drug. By simultaneously blocking the reuptake of dopamine, noradrenaline, and serotonin it curbs hunger and increases satiety, and it additionally silences appetite-driving GABAergic neurons in the hypothalamus. In a phase 2 obesity trial it produced weight loss roughly twice that of the obesity medications approved at the time, though that trial has carried an expression of concern over its adverse-effect reporting since 2013; it remains investigational, with cardiovascular effects among the safety considerations.
Pinealon is a synthetic tripeptide bioregulator (Glu-Asp-Arg, also called the EDR peptide) from the Russian Khavinson family of short peptides, developed to support the brain and target age-related cognitive decline [1][5]. In laboratory and animal studies it acts as a neuroprotective agent that shields neurons from oxidative stress and hypoxia, promotes healthy dendrite growth, and helps regulate the genes that keep neurons functioning [1][3]. Marketed as a peptide geroprotector for memory and healthy brain aging, it is one of the best known members of the short-peptide nootropic class [4][5].
MNT (PMP) is a combination injectable and pre-workout formula that pairs nitric oxide precursors with a focused cognitive stack in a single shot. Arginine, citrulline, and the arginase inhibitor norvaline drive vasodilation and blood flow for a stronger pump, while citicoline, N-acetyl-L-tyrosine, and trimethylglycine sharpen focus and support drive under load. It is engineered as a two-in-one performance blend that delivers physical pump and mental clarity together.
RGPU-95 is an experimental compound studied in Russian pharmacological research as a structural analog of fenotropil, better known as phenylpiracetam, a nootropic of the racetam family. In animal experiments it has shown anxiety-reducing and antidepressant-like effects, in some measures exceeding those of its parent compound. It is an obscure investigational substance with essentially no human data, and it is not an approved medicine or recognized supplement ingredient anywhere.
7,8-Dihydroxyflavone (7,8-DHF), also called tropoflavin, is a naturally occurring flavone studied as a small-molecule mimic of brain-derived neurotrophic factor (BDNF). It is reported to act as an agonist of tropomyosin receptor kinase B (TrkB), the principal BDNF receptor, binding the receptor's extracellular domain to drive its dimerization and activation, and because it is orally active and crosses the blood-brain barrier it has become a widely used tool compound in neuroscience. Its direct activation of TrkB is not fully settled, however, since some quantitative assays have been unable to reproduce it, and it remains an experimental compound studied in models of depression, Alzheimer's, and other neurological conditions.
ACP-105 is a potent nonsteroidal selective androgen receptor modulator (SARM) engineered to deliver the muscle- and bone-building benefits of androgens with greater tissue selectivity than testosterone. As a partial agonist at the androgen receptor, it was designed to drive anabolism in muscle and bone while limiting the unwanted effects tied to classic steroids. Its combination of anabolic potency and an intriguing signal for cognitive and neuroprotective effects has made it a standout among research-grade SARMs.
Agmatine is a small biogenic amine produced in the body from the amino acid arginine by the enzyme arginine decarboxylase, and it also occurs in fermented foods. Rather than acting on a single dedicated receptor, it is a neuromodulator that engages several systems at once: it is an endogenous ligand at imidazoline receptors, blocks the open pore of the NMDA glutamate receptor, and inhibits neuronal nitric oxide synthase, in part by acting as a suicide substrate that irreversibly destroys the enzyme's heme. It is studied for possible roles in pain, mood, opioid tolerance, and neuroprotection, and is sold as a dietary supplement in the form of agmatine sulfate.
American ginseng (Panax quinquefolius) is a slow-growing perennial herb of the ivy family, native to the hardwood forests of eastern North America and prized for its aromatic root. It has been harvested and traded for centuries, especially for export to East Asia, where it is used in traditional medicine and valued as a tonic distinct in character from Asian ginseng. Its roots contain ginsenosides, and modern research has examined it for effects on blood sugar, cognition, cancer-related fatigue, and the common cold [1][2].
Ampasse is a Russian intravenous nootropic, the calcium salt of 5-hydroxynicotinoyl glutamate, presented as an ampakine that modulates AMPA type glutamate receptors in chronic cerebrovascular disease.
Artichoke extract is a botanical preparation made from the leaves of the globe artichoke (Cynara cardunculus var. scolymus), a cultivated thistle in the family Asteraceae. It is standardized for polyphenols such as cynarin, chlorogenic acid, and the flavone luteolin, and has a long history of use as a digestive aid and bile stimulant. Modern research has focused mainly on its modest cholesterol-lowering and liver-supportive effects, while a niche nootropic interest stems from luteolin's ability to inhibit phosphodiesterase enzymes.
Biotredin is a Russian sublingual tablet of L-threonine with vitamin B6, taken for mental performance and for alcohol withdrawal.
BrainMax is a Russian two ingredient capsule combining meldonium with emoxypine succinate, sold for fatigue, attention and recovery after illness; both ingredients have a substantial Russian literature and essentially no independent international evidence.
Bupropion is an atypical antidepressant of the aminoketone class that works mainly as a norepinephrine-dopamine reuptake inhibitor. It is used to treat major depressive disorder and seasonal affective disorder and, under a separate brand, as an aid to quitting smoking; it is also part of a combination weight-loss product. Unlike many antidepressants it has little direct effect on serotonin and rarely causes sexual dysfunction or weight gain.
Cacao powder is the ground, mostly de-fatted solids of the roasted Theobroma cacao bean. Its active fraction is a group of flavanols (flavan-3-ols), chiefly (-)-epicatechin and catechin plus procyanidins, alongside the methylxanthine theobromine and a little caffeine. The flavanols drive nitric-oxide-dependent vasodilation, which is the best-supported reason people take it: lower blood pressure, better endothelial function, and modestly improved blood flow to the brain. Natural (non-alkalized) cacao keeps far more of these flavanols than Dutch-processed cocoa.
Caffeine sodium benzoate is the water soluble form of caffeine used across Russian medicine as a stimulant and respiratory analeptic, and as the caffeine component of combination headache tablets.
Chlodantane is an adamantane-derived adaptogen developed in Russian pharmacology to rapidly boost the body's resistance to physical, chemical, and thermal stress. A close relative of bromantane, it pairs fast-acting adaptogenic effects with immune-stimulating, membrane-protective activity. For those interested in stress resistance and resilience compounds, chlodantane is an intriguing member of the adamantane family.
Choline bitartrate is a salt of the essential nutrient choline combined with tartaric acid, widely used as an inexpensive dietary supplement to boost choline intake [1][2]. Because choline supports cell membranes, the neurotransmitter acetylcholine, and methyl-group metabolism, the bitartrate form is taken to help meet the body's need for the nutrient [1][3]. It is a common choice in supplements, valued for being stable and absorbing little moisture, and it delivers choline for the same functions as choline from food [1]. As with choline generally, very high intakes can cause side effects such as a fishy body odor [1].
CMS-121 is an experimental drug created by chemically redesigning fisetin, a plant flavonoid; the result is a synthetic quinoline rather than a flavonoid itself, and it is not the same substance as fisetin. In animals it blocks fatty acid synthase, an enzyme that builds fats, and this reduces oxidative damage to the fats in cell membranes; treated mice held onto memory better in models of Alzheimer's disease, Huntington's disease and accelerated ageing, and also showed improved blood sugar and body weight. Human evidence is limited to a single Phase 1 study in 99 healthy volunteers that asked only whether the drug was tolerated and how the body handled it, not whether it helps anyone; that report remains an unpublished preprint. Almost all of the animal work comes from the one laboratory that invented the compound, no human being has ever been tested for a benefit, and CMS-121 is not approved anywhere for any use.
Cytoflavin is a Russian four component metabolic preparation of succinic acid, inosine, nicotinamide and riboflavin, given as enteric tablets or intravenous infusion for cerebral ischaemia and encephalopathy.
Dehydroepiandrosterone (DHEA) is an endogenous androstane neurosteroid and the most abundant circulating steroid hormone in humans, secreted chiefly by the adrenal cortex and also synthesized de novo within the central nervous system. It functions primarily as a precursor to androgens and estrogens, yet exerts direct actions on the brain by acting as an agonist at the sigma-1 receptor (an endoplasmic reticulum chaperone protein that shapes calcium and neurotrophic signaling), as a positive modulator of NMDA receptor (the principal excitatory glutamate ion channel involved in learning) signaling, and, chiefly as its sulfate ester DHEAS, as a negative allosteric modulator of the GABA-A receptor (the brain's main inhibitory ion channel). DHEA additionally behaves as a functional anti-glucocorticoid, buffering the neurotoxic effects of cortisol, and shows neuroprotective and mood-related activity in preclinical and clinical studies. Circulating concentrations peak in early adulthood and decline markedly with age, a phenomenon termed adrenopause that has driven its widespread use as an over-the-counter supplement.
Divaza is a Russian lozenge from Materia Medica containing so-called release-active antibodies to S-100 protein and to endothelial nitric oxide synthase; these are homeopathic ultra-dilutions rather than measurable quantities of antibody.
Dimethylaminoethanol (DMAE), also known as deanol or dimethylethanolamine, is an organic amino alcohol with the formula (CH3)2NCH2CH2OH. Structurally it resembles the nutrient choline, differing by one methyl group on its nitrogen atom, and it is chemically related to the neurotransmitter acetylcholine. Alongside a range of industrial uses, DMAE is sold as a dietary supplement promoted for cognition and mood and is used as an ingredient in skin-firming cosmetics, although the evidence for many of its claimed effects is limited.
Etifoxine (brand name Stresam; also called etafenoxine) is a benzoxazine anxiolytic (an anti-anxiety drug from a chemical family unrelated to the benzodiazepines like Valium). It has been prescribed for the anxious, tense, physical side of stress mainly in France and a handful of other countries since the late 1970s, and it is not approved by the US FDA. What makes it interesting is a dual mechanism: it calms the brain both by directly tuning up GABA-A receptors and by nudging the body to make more of its own calming neurosteroids. In head-to-head trials it eased anxiety comparably to some benzodiazepines while causing less sedation, less memory and psychomotor impairment, and little rebound or dependence when stopped. It has also been explored beyond anxiety for helping injured peripheral nerves heal and for damping neuroinflammation (inflammation inside nervous tissue). The important caveat is safety: rare but serious liver injury and severe skin reactions have been reported.
Eutropoflavin is a synthetic flavonoid studied as a selective agonist of TrkB, the receptor for brain-derived neurotrophic factor (BDNF). Chemically known as 4'-dimethylamino-7,8-dihydroxyflavone, it is a modified and more potent derivative of tropoflavin (7,8-dihydroxyflavone). In animal experiments it activates TrkB more strongly and for longer than its parent compound and shows neuroprotective, neurogenic, and antidepressant-like effects. It is not an approved medicine, although it has been sold online as a nootropic.
FGL is a synthetic 15-residue peptide copying the loop that the neural cell adhesion molecule (NCAM) uses to switch on FGFR1 growth-factor signalling. In rodents it has sharpened learning and memory, strengthened synaptic transmission, and protected hippocampal neurons against amyloid-beta, ischemia and injury. Its dimeric form cleared a single-dose phase 1 study in 24 healthy men and the announced Alzheimer's trial never followed, so every efficacy claim on this page is still an animal claim. Two findings sit against the promise: it lowered the seizure threshold in a kindling model, and it reduced neuron counts in uninjured brains.
Fisetin is a naturally occurring flavonoid, specifically a flavonol, found in fruits and vegetables such as strawberries, apples and onions. It is a yellow plant pigment that acts as an antioxidant and has drawn scientific interest for its potential effects on aging, including an ability to clear senescent cells. It is sold as a dietary supplement, though clinical evidence of benefit in humans remains limited.
Forskolin is a natural compound belonging to the labdane diterpenes, extracted from the roots of the Indian coleus plant (Plectranthus barbatus, also known as Coleus forskohlii). It is best known in biology as a laboratory tool because it directly switches on the enzyme adenylyl cyclase, raising cellular levels of the messenger molecule cAMP. The plant has a history in traditional Ayurvedic medicine, and forskolin is also sold as a dietary supplement, often marketed for weight loss, though the evidence for that use is weak. In research it is prized for its ability to raise cAMP in almost any cell without needing a specific receptor.
Fursultiamine, also called TTFD, is a man-made form of vitamin B1 in which the vitamin is joined to a fatty side group, so it crosses membranes without needing the saturable transporter that caps how much ordinary thiamine the gut can absorb; once inside a cell the bond is cut and plain thiamine is released. It is an approved medicine in Japan, where it has been used since 1961 for beriberi, vitamin B1 deficiency and Wernicke encephalopathy, and for those jobs it works. The popular claims that it lifts energy, focus or mood in people who are not deficient rest on very thin evidence; there is one small crossover trial in athletes, one uncontrolled 12 week study in Alzheimer's patients and an open pilot in ten autistic children, with no modern randomised trial for any cognitive endpoint. It does have one genuinely non-vitamin action, blocking the hormone hepcidin at a cysteine on the iron exporter ferroportin, but that effect vanished in live mice because the compound breaks down to ordinary thiamine within about an hour.
Ginkgo biloba, commonly called the maidenhair tree, is a gymnosperm native to East Asia and the sole surviving species of the order Ginkgoales, an ancient lineage often described as a living fossil. Standardized extracts of its distinctive fan-shaped leaves, rich in flavonoid glycosides and terpene trilactones, are among the most widely used herbal products worldwide. They are marketed chiefly to support memory and circulation, though clinical evidence for cognitive benefit remains contested.
Nootrop is a capsule blend of glycine with gotu kola and ginkgo biloba extracts and four B vitamins, sold as a general cognition and calm supplement.
Gotu kola is the common name for Centella asiatica, a small creeping herbaceous plant of the family Apiaceae that grows in wetlands across Asia and other warm regions. It has a long history in Ayurvedic and traditional Chinese medicine, where it has been used for wound healing, skin conditions, and as a tonic said to support memory and mental clarity. Its activity is attributed to a group of pentacyclic triterpenoid compounds, including asiaticoside, madecassoside, and their related acids.
Guarana is a climbing plant native to the Amazon basin, classified as Paullinia cupana in the soapberry family Sapindaceae, whose seeds are prized for an unusually high caffeine content. Indigenous peoples of the region, including the Sateré-Mawé, have long processed the seeds into a dried paste used to brew a stimulating beverage. Today the seed powder and its extracts are used chiefly as a caffeine source in soft drinks, energy drinks, and dietary supplements.
Hopantenic acid, best known by the Russian brand Pantogam and as its calcium salt calcium hopantenate, is a naturally occurring homologue of pantothenic acid in which the beta-alanine unit is replaced by GABA [1]. It is used in Russia and formerly in Japan as a gentle nootropic and mild anxiolytic-anticonvulsant, particularly in children with cognitive, behavioral and hyperkinetic problems [1][2]. Its effects are attributed to weak GABA-B-like modulation combined with support of neuronal metabolism, and the bulk of its clinical evidence is Russian rather than from large Western trials [1].
Hydrafinil, also called 9-fluorenol or 9-hydroxyfluorene, is a simple laboratory chemical that Cephalon tested around 2012 while looking for a successor to the wakefulness drug modafinil; despite the similar sounding name it is not chemically related to modafinil and belongs to a different chemical family. In the single rat experiment that exists it kept animals awake longer than modafinil did at the same injected dose, after which the programme was dropped with no published reason and never reached a human trial. The entire human record is one anti-doping study in which three healthy men each swallowed a single 50 mg dose so that laboratories could learn to detect it in urine; nothing at all has been published on whether it improves alertness, attention or fatigue in people, and nothing has been published on its safety. It is banned in competition by the World Anti-Doping Agency and is not an approved medicine in any country.
Ipidacrine is a genuine Cold War-era Soviet original, synthesized at the National Research Center for Biologically Active Compounds in Russia and pushed through the 1970s and 1980s under the code name NIK-247, decades before it ever appeared on a Western researcher's radar. Rather than working through the single acetylcholinesterase-inhibition mechanism most of its Western contemporaries relied on, it combines that AChE blockade with direct potassium-channel blockade at nerve and muscle membranes, a dual action that boosts both central cholinergic tone and peripheral nerve-impulse conduction. It remains sold and prescribed today in Russia and several post-Soviet states as Neuromidin (also called Amiridin or, in a topical form, Axamon), for memory disorders and peripheral nerve conditions, but it never went through Western-style FDA or EMA trials and stayed essentially invisible outside that regulatory sphere, a working drug that the rest of the world simply never met.
L-serine is a proteinogenic alpha-amino acid that the body can normally synthesize, which classifies it as non-essential, though this label is increasingly viewed as conditional. Built mainly from an intermediate of glucose metabolism, it sits at a hub of one-carbon metabolism, supplying building blocks for proteins, the amino acids glycine and cysteine, cell-membrane lipids, and nucleotides, as well as the NMDA-receptor co-agonist D-serine. When L-serine is scarce, the enzyme serine palmitoyltransferase incorporates alanine in its place and produces neurotoxic 1-deoxysphingolipids, the biochemical cause of hereditary sensory and autonomic neuropathy type 1; oral L-serine reduces their formation and is used as a treatment for that disorder. It is also under study for a range of other neurological conditions and is available as a dietary supplement.
L-Theanine is a non-proteinogenic amino acid found almost exclusively in the tea plant Camellia sinensis, where it contributes part of brewed tea's savory taste. Chemically it is N-ethyl-L-glutamine, a structural analog of the neurotransmitter glutamate that crosses the blood-brain barrier and interacts with glutamate receptors, weakly modulating NMDA receptors and inhibiting binding at AMPA/kainate sites, while also raising dopamine and other monoamines; on EEG it increases alpha brain-wave activity, the signature of a relaxed but alert state. It is widely used as a supplement for relaxation, attention, and sleep, and is often paired with caffeine, with which it shows a well-studied synergy on attention, although the overall strength of the clinical evidence is still debated.
Lemon balm, known botanically as Melissa officinalis, is a lemon-scented perennial herb in the mint family, Lamiaceae. Native to the eastern Mediterranean and western Asia, it has been grown for over two thousand years and used traditionally to ease tension, lift mood, and aid digestion and sleep. Its leaves are rich in the polyphenol rosmarinic acid and in fragrant terpenes such as citronellal, geranial, and neral. Modern controlled studies have examined it for anxiety, mood, cognition, sleep, and palpitations, with its calming effect attributed largely to rosmarinic acid inhibiting GABA transaminase and to extract binding at cholinergic receptors.
Maritupirdine is a multi-receptor antagonist approved in Russia in 2023 as Aviandr for generalised anxiety disorder; it was originally developed by Avineuro as a 5-HT6 antagonist for Alzheimer's disease.
MCT oil is a fat made of medium-chain triglycerides, usually the C8 (caprylic) and C10 (capric) fatty acids fractionated out of coconut or palm kernel oil. Unlike normal dietary fat, these shorter chains skip the lymphatic route and travel straight to the liver via the portal vein, where they're burned fast and partly converted to ketone bodies. That gives a quick alternative fuel for muscle and brain, a small bump in energy expenditure, and a mild satiety effect.
Mebicar is a Latvian anxiolytic built on a bicyclic urea scaffold, taken for anxiety, irritability and nicotine withdrawal without the sedation or motor impairment of a benzodiazepine.
Methylcobalamin, also called mecobalamin, is a naturally occurring form of vitamin B12 in which the cobalt atom carries a methyl group. It is one of the two coenzyme forms of the vitamin that are active in the human body, serving as an essential cofactor for the enzyme methionine synthase. Methylcobalamin is used as a dietary supplement and, in some countries, as a medicine, and it can prevent or correct vitamin B12 deficiency in the same way as other B12 forms.
Power Duo ModaXL is a 250 mg tablet said to contain both modafinil and armodafinil in a single dose.
N-Acetyl L-Tyrosine (NALT) is an acetylated, more water-soluble form of the amino acid L-tyrosine, originally introduced as a tyrosine source for intravenous nutrition. It is widely marketed as a nootropic on the premise that tyrosine is the precursor of the catecholamine neurotransmitters dopamine and norepinephrine. However, human and animal studies indicate that N-Acetyl L-Tyrosine is converted to free tyrosine inefficiently, with much of an infused dose excreted unchanged in the urine.
nicergoline (sermion) is a semisynthetic ergoline nootropic-vasodilator; a potent alpha-1 blocker that also boosts cholinergic/neurotrophic tone, with modest but real cochrane-backed benefit in age-related and vascular cognitive decline, tempered by ergot-class fibrosis risk on long timelines.
Nobiletin is a polymethoxylated flavone, a type of plant flavonoid distinguished by several methoxy groups attached to its ring structure. It occurs naturally in the peels of citrus fruits, being especially abundant in tangerines and related species. Laboratory and animal research has examined it for anti-inflammatory, metabolic, and neuroprotective activity, and more recently for its ability to influence the body's circadian clock. It is a dietary constituent and research compound rather than an approved medicine.
Nooglutyl (N-(5-hydroxynicotinoyl)-L-glutamic acid) is a memory-oriented nootropic developed at the Zakusov Institute of Pharmacology, the Russian laboratory also associated with Noopept and Semax. Radioligand studies identify it as a direct positive modulator of AMPA-subtype glutamate receptors, competing with selective AMPA agonists at low micromolar concentrations, which links it mechanistically to the fast excitatory signaling that underlies learning and synaptic plasticity. Across diverse rodent models of amnesia, including those induced by hypoxia, electroconvulsive shock, and cerebral trauma, it produced consistent anti-amnesic effects, and it additionally displayed neuroprotective, antihypoxic, and antioxidant activity in models of ischemic and hemorrhagic stroke. Notably, it improved behavior and memory retrieval in senescence-accelerated (SAMP10) mice, extending interest toward age-related cognitive decline. It remains an investigational compound characterized largely in preclinical research.
Orexin-A, also known as hypocretin-1, is a 33-amino-acid neuropeptide produced by a small population of neurons in the lateral hypothalamus that is central to promoting wakefulness and arousal. It is one of two orexin peptides cut from a single precursor and signals through two G-protein-coupled receptors. Narcolepsy type 1 is essentially an orexin-deficiency disease, in which the roughly 70,000 orexin-producing neurons are selectively destroyed and cerebrospinal-fluid orexin becomes undetectable; this is the rationale for orexin-2 receptor agonists now in clinical trials as the first mechanism-based, replacement-style treatment rather than a symptomatic stimulant. Since its discovery in 1998 the orexin system has become a major target in sleep medicine.
Orexin-A fragment 17-33 is a shortened, C-terminal portion of the neuropeptide orexin-A, comprising the last seventeen of its thirty-three amino acids. It belongs to a group of truncated orexin peptides studied to map which parts of the parent molecule are needed to activate orexin receptors. Research on such fragments showed that the activity of orexin-A resides mainly in its C-terminal end, and the fragment is used chiefly as a laboratory tool for probing the orexin system rather than as a medicine.
Orexin-B, also known as hypocretin-2, is a 28-amino-acid neuropeptide made in the hypothalamus that, together with orexin-A, promotes wakefulness, arousal, and appetite. It is cut from the same precursor as orexin-A but lacks internal disulfide bonds and preferentially activates the orexin type 2 receptor. That receptor is the target of the dual orexin receptor antagonists suvorexant, lemborexant, and daridorexant, which treat insomnia by blocking the same signaling whose loss causes narcolepsy, making the two conditions pharmacological mirror images; one of these drugs was also reported to acutely lower tau and amyloid-beta in human cerebrospinal fluid. The orexin system was discovered in 1998.
Peptide Complex Pro 02 is a leave on skin lotion combining a brain tissue peptide extract with a ginseng derived antioxidant complex and grapefruit oil, sold for the nervous system; it is a topical mixture rather than a peptide of known sequence.
Phenylpiracetam Hydrazide (fonturacetam hydrazide) is a structural variant of phenylpiracetam in which the racetam's amide group is replaced by a hydrazide, marketed as a next-generation twist on one of the most potent racetam nootropics [4]. Its appeal rests on the phenylpiracetam framework, a scaffold known for selective dopamine transporter inhibition and stimulant-like focus, endurance, and cold resistance [2][5]. It is sold strictly as a research chemical, and its own pharmacology has not been characterized in published human or animal studies, so its profile is inferred from the phenylpiracetam parent it is built upon [3][4].
Phosphatidylcholine is a class of phospholipids that form a major part of the membranes surrounding living cells and are the principal component of lecithin. Each molecule is built from a glycerol backbone, two fatty acids, and a phosphate group linked to choline, and the compound is abundant in foods such as egg yolk and soybeans. Beyond its structural role, phosphatidylcholine is the body's main store of the essential nutrient choline and has been studied as a dietary supplement and in conditions ranging from liver disease to ulcerative colitis.
Phosphatidylserine is a phospholipid that is a normal building block of cell membranes, where it is concentrated on the inner surface and is especially abundant in the membranes of nerve cells. It takes part in cell signaling and blood clotting, and its externalization onto the cell surface serves as the principal signal that flags dying cells for removal, a signal that some tumors and pathogens exploit to evade immune clearance. As a dietary supplement, usually derived from soy or sunflower, it is marketed chiefly for memory and age-related cognitive decline and has been reported to blunt the cortisol response to stress, although the supporting evidence for cognitive benefit is regarded as limited.
Omaron is a fixed combination of 400 mg piracetam and 25 mg cinnarizine, sold across the CIS for cerebrovascular complaints and vertigo.
Piritinol, also spelled pyritinol and known as pyrithioxine, is a semisynthetic derivative of vitamin B6 (pyridoxine) that has been used as a nootropic and cerebral-function agent since the 1960s. It is built from two pyridoxine molecules linked by a disulfide bridge, a change that alters how the molecule behaves compared with the parent vitamin. In several European countries it is prescribed for chronic cognitive impairment and as supportive care after head trauma, and it has also been sold as a dietary supplement in some markets.
Rasagiline is a prescription tablet for Parkinson's disease that permanently switches off monoamine oxidase B, the enzyme that breaks down dopamine in the brain; the effect is to make what dopamine remains last longer. Four large placebo-controlled trials show a real but modest symptom benefit, whether taken alone in early disease or added to levodopa later, where it removes roughly one hour per day of the time when levodopa is not working. Whether it actually slows the disease itself is unsettled; in the ADAGIO trial the 1 mg dose met all three of its targets while the 2 mg dose failed them, and that contradiction was never resolved. Trials in multiple system atrophy and in ALS were negative, and no evidence supports rasagiline as a cognitive enhancer in healthy people.
Revilab SL 02 is a sublingual drop combining brain, retina and vascular peptide extracts with herbal extracts and essential oils, sold for the nervous system and vision; it is a proprietary mixture rather than a peptide of known sequence.
Rhodiola rosea, commonly called golden root or roseroot, is a perennial flowering plant of the family Crassulaceae that grows in cold, high-altitude and Arctic regions. Its root has a long history of use in the traditional medicine of northern Europe and Asia, and it is popularly classed as an adaptogen, an herb said to help the body resist stress and fatigue. Its most characteristic studied constituents are the phenolic compounds rosavin and salidroside, though high-quality clinical evidence for its benefits is limited.
Rosemary extract is a concentrated preparation of the culinary herb Rosmarinus officinalis (now often classed as Salvia rosmarinus). Its active fraction is dominated by two polyphenols; carnosic acid, a fat-soluble diterpene that activates the body's own antioxidant defenses, and rosmarinic acid, a water-soluble caffeic acid ester. The plant's volatile oil also carries 1,8-cineole, the aromatic component tied to rosemary's cognitive reputation. It's studied mostly for memory support, antioxidant activity, and mild mood effects.
Salicin is an alcoholic beta-glucoside and a principal salicylate of willow (Salix) and poplar bark and meadowsweet, historically valued as a botanical analgesic and the conceptual forerunner of aspirin. Following ingestion it is hydrolyzed and oxidized to salicylic acid, the same active metabolite that mediates aspirin's effects, though at doses that spare much of the gastric irritation associated with acetylsalicylic acid. Mechanistic studies attribute its anti-inflammatory and antioxidant actions to suppression of the NF-kappaB and MAPK signaling pathways and activation of the Nrf2-heme oxygenase-1 axis, with additional contributions from co-occurring polyphenols and downstream catechol metabolites; salicin has also been identified as an agonist of the bitter taste receptor TAS2R16, a receptor-mediated route to resolving inflammation. Standardized willow bark preparations are used mainly for musculoskeletal and inflammatory pain, and their clinical activity is not fully accounted for by salicin content alone.
SAM-e is a molecule the body already makes from the amino acid methionine; it is the chemical the body uses to hand a methyl group to hundreds of enzymes, which is how it reaches DNA, brain chemicals such as dopamine, and liver metabolism. It is sold as a dietary supplement in the United States and as a prescription drug called ademetionine in Italy, Germany and Russia, mostly for depression, joint pain and liver problems. The evidence is real but genuinely mixed; the Cochrane review of eight trials found the quality too low to draw a conclusion, the largest United States trial found SAM-e no better than placebo, and two separate 2024 meta-analyses of much the same studies reached opposite answers. It is usually well tolerated apart from stomach upset, but it can trigger mania in people with bipolar disorder and should not be combined casually with antidepressants.
Selank + Semax is a nasal spray pairing two Russian research peptides that are normally sold on their own. Selank is a synthetic relative of the immune peptide tuftsin, studied in Russia as an anxiolytic that does not sedate and does not appear to produce the tolerance or withdrawal that benzodiazepines do. Semax is a shortened fragment of ACTH, cut so that it keeps the behavioural effects without the hormonal ones, and studied for attention, stroke recovery and neuroprotection. Both are reported to raise BDNF, and that shared thread is the usual argument for combining them: one takes the edge off, the other sharpens.
Sipagladenant (development code KW-6356; CAS 858979-50-7) is an investigational, orally active, highly selective antagonist and inverse agonist of the adenosine A2A receptor developed by Kyowa Kirin for Parkinson's disease. It belongs to the non-dopaminergic class of antiparkinsonian agents typified by istradefylline, but in vitro studies distinguish it by insurmountable antagonism, very slow receptor dissociation, and inverse-agonist activity that suppresses the constitutive signaling of the A2A receptor. Because A2A receptors are densely co-expressed with dopamine D2 receptors as A2A-D2 heteromers on striatopallidal neurons of the indirect motor pathway, blockade of A2A relieves the adenosine-mediated brake on D2 signaling and improves motor output without directly stimulating dopamine receptors. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treated marmosets it reversed motor disability as monotherapy, produced greater anti-parkinsonian activity than istradefylline, and potentiated levodopa with a low propensity to induce dyskinesia; a placebo-controlled trial in early, untreated Parkinson's disease reported improvement in MDS-UPDRS Part III scores. Sipagladenant remains a clinical-stage compound; it is not approved for any indication, and much of its long-term efficacy and safety profile is still being characterized.
Spermidine is a naturally occurring polyamine, a small organic molecule found in all living cells and in many foods such as wheat germ, aged cheese, soybeans, and mushrooms. First isolated from semen, which gives it its name, it plays fundamental roles in cell growth, gene regulation, and membrane stability. In recent years it has attracted attention as a potential longevity compound because it triggers autophagy, the cellular recycling process linked to healthy aging.
Taurine is a sulfur-containing amino sulfonic acid, related to the amino acids but not used to build proteins, and it is especially abundant in the brain, heart, muscle, and retina. Beyond its familiar roles in bile-salt formation, osmoregulation, and antioxidant defense, cells use taurine to chemically modify mitochondrial transfer RNA, attaching it at the anticodon wobble position so that certain codons are read correctly; this was the first evidence that taurine is a building block of a biological macromolecule, and losing the modification is the molecular cause of the mitochondrial diseases MELAS and MERRF. Obtained in the diet mainly from meat and seafood, it is a common ingredient in energy drinks and dietary supplements and is studied for cardiovascular, metabolic, and aging-related effects.
Theacrine is a naturally occurring purine alkaloid, chemically 1,3,7,9-tetramethyluric acid, that is closely related to caffeine and found in the leaves of kucha tea (Camellia assamica var. kucha) and in the cupuacu fruit. It has stimulant-like properties and, like caffeine, acts on adenosine and dopamine signaling to influence energy, alertness, and locomotor activity [1]. Sold as a dietary supplement, often under the trade name TeaCrine, it has drawn attention as a longer-acting alternative to caffeine that appears less prone to tolerance with repeated use [2].
Unifiram (DM232) is an exceptionally potent synthetic nootropic developed by Italian medicinal chemists as a next-generation cognition enhancer. Structurally related to the ampakines and to piracetam, it was reported in preclinical studies to be roughly four orders of magnitude more potent than piracetam at reversing memory impairment. This remarkable potency, paired with an ampakine-like boost to learning circuitry, has made unifiram a headline compound in the research-chemical nootropic scene.
Uridine is a nucleoside, one of the building blocks of ribonucleic acid (RNA), formed from the base uracil joined to the sugar ribose. It occurs naturally in the body, where it can be made from scratch, and in foods, and it takes part in RNA synthesis, sugar metabolism and the production of cell-membrane phospholipids. As a supplement, usually in the form of uridine monophosphate, it has been studied for effects on brain phospholipids, memory and mood [1][3].
Uridine monophosphate (UMP) is the nucleotide form of uridine and the most common way uridine is sold as a nootropic. It feeds the pathway that builds neuronal membranes and supports acetylcholine and dopamine signaling; it is the uridine in the popular Mr Happy stack alongside omega-3s and a choline source.
Uridine triacetate is a prodrug of uridine; three acetate groups make it far more orally bioavailable than plain uridine, so it delivers much more uridine to the body and brain. It is used both clinically (as Vistogard/Xuriden) and popularly in nootropic uridine stacks for memory and mood.
Vinpotropile is a Russian fixed combination of vinpocetine and piracetam sold for cerebrovascular complaints and memory problems.
Pramiracetam is a laboratory-made compound in the piracetam ("racetam") family, developed by Parke-Davis as CI-879 and later sold in a few European countries as a prescription memory drug under the brand name Pramistar. It is meant to improve memory and attention; in animals it reliably increases the rate at which brain cells take up choline, a building block of the memory-related signalling chemical acetylcholine, but no receptor that it binds to has ever been identified. Human evidence is thin: a small placebo-controlled trial in men with head injuries reported better delayed recall, and a study in healthy volunteers found it partly blunted drug-induced forgetting, while a trial in Alzheimer's disease found no benefit even at high doses. The entire published literature is roughly 40 papers, most of them small, decades old, or done in rodents, so confident claims that it strongly enhances cognition in healthy people are not supported by what has actually been measured.
Sunifiram (DM-235) is a synthetic nootropic structurally related to piracetam but dramatically more potent, active at very low doses. It enhances learning and memory by acting on the glycine site of the NMDA receptor and strengthening AMPA-mediated signaling through the CaMKII and PKC pathways, the molecular basis of long-term potentiation. In animal studies it improves cognition and reverses drug-induced amnesia at doses roughly a thousandfold lower than classic racetams, making it one of the most potent research nootropics of its kind.
IDRA-21 is a small synthetic molecule derived from the blood pressure drug diazoxide. It does not switch brain receptors on by itself; instead it makes the AMPA receptor, which handles the brain's main fast excitatory signal, stay open longer once that natural signal arrives. Oral dosing improved memory scores in rats and in three separate monkey studies, which is why it is sold as a research chemical marketed for cognition. The evidence stops there; no person has ever been studied in a published trial, no clinical trial is registered, and no dose, blood level or side effect profile in humans has ever been reported. One rat study found it made hippocampal cell death after a stroke-like insult worse rather than better, so the safety picture is genuinely open.
Thozalinone is a classic oxazolinone psychostimulant from the same chemical family as pemoline, originally developed in the 1960s as a mood-lifting antidepressant and appetite suppressant. It delivers amphetamine-like central stimulation and energizing, drive-boosting effects through dopaminergic pathways. A largely forgotten agent of the early psychopharmacology era, it has drawn renewed curiosity as a stimulant research chemical.
MPAP is an experimental laboratory chemical from the Hungarian "enhancer" series that also produced PPAP and BPAP; it is a chemical relative of the amphetamines but it does not work like one, since it does not force neurotransmitter out of nerve cells. In rats it appears to make catecholamine and serotonin neurons release a little more transmitter when those neurons are already firing, and it did so at about one fifth of the dose PPAP required; that single set of animal experiments is essentially the entire evidence base. There are no human studies, no established dose, no safety or toxicology data, and no measured binding constants for MPAP, and the popular explanation of how it works (TAAR1 activation) comes from experiments on its cousin BPAP rather than on MPAP. It is best read as a compound whose profile is inferred by analogy; the confident descriptions of it circulating online outrun the actual data by a wide margin.
Lion's Mane is the common name for Hericium erinaceus, an edible and medicinal mushroom recognized by its cascade of long, white, icicle-like spines. Native to North America and Eurasia, it grows on hardwood trees and has long been used as food and in traditional Chinese medicine. It is now sold widely as a dietary supplement marketed for brain and nerve health, though human evidence remains limited.
Citicoline with piracetam is a combination of two nootropic compounds sometimes taken together for cognitive support. Citicoline, also called cytidine diphosphate choline, is a naturally occurring precursor used to build brain cell membranes and the neurotransmitter acetylcholine, while piracetam is a synthetic derivative of GABA and the original member of the racetam family. The pairing is popular in nootropic circles, although the two ingredients have been studied mainly on their own rather than as a fixed combination.
Losartan is an angiotensin II receptor blocker (ARB) used mainly to treat high blood pressure and to protect the kidneys in people with type 2 diabetes. It was the first drug of its class to reach the market, working by blocking the angiotensin II type 1 (AT1) receptor so that blood vessels relax and the heart and kidneys face less strain. Taken by mouth as the potassium salt, it is now a widely available, low-cost generic on the World Health Organization list of essential medicines.
Intranasal insulin is an experimental way of giving insulin as a nasal spray so that it reaches the brain directly, largely bypassing the bloodstream. It is studied mainly as a potential treatment for memory disorders such as Alzheimer's disease and mild cognitive impairment, on the idea that boosting insulin signaling in the brain might support cognition. It is not an approved therapy; early studies were encouraging, but the largest trial to date did not show a clear benefit.
Amphetamine is a potent central nervous system stimulant and the parent compound of a broad family of related drugs. In medicine it is used chiefly to treat attention-deficit hyperactivity disorder (ADHD) and narcolepsy, where it improves attention, wakefulness, and impulse control by raising the brain's levels of the neurotransmitters dopamine and norepinephrine [1]. It also has a long history of recreational misuse and a potential for dependence, and it is tightly regulated as a controlled substance in most countries [1].
Dexmethylphenidate is a central nervous system stimulant used to treat attention deficit hyperactivity disorder (ADHD). It is the more active of the two mirror-image forms of methylphenidate, specifically the d-threo enantiomer, and is sold under the brand name Focalin in immediate-release and extended-release forms. By blocking the reuptake of dopamine and norepinephrine, it raises the availability of these neurotransmitters in the brain. In the United States it is a Schedule II controlled substance available only by prescription.
Dextroamphetamine is a central nervous system stimulant and the more active of the two mirror-image forms of amphetamine. It is used mainly to treat attention deficit hyperactivity disorder (ADHD) and narcolepsy, and it forms the active component of several widely prescribed medicines, including Dexedrine, the mixed-salt product Adderall, and the prodrug lisdexamfetamine. The drug works by increasing the release and availability of the neurotransmitters dopamine and norepinephrine in the brain. Because it carries a risk of dependence and misuse, it is a Schedule II controlled substance in the United States.
HBT1 is a positive allosteric modulator of the AMPA receptor (an "ampakine") that came out of a Takeda drug-discovery program. Its selling point is a gentler profile than earlier ampakines; it has low intrinsic agonist activity and works mostly only when the brain's own glutamate is present, which let it raise BDNF (brain-derived neurotrophic factor, a key growth signal for neurons) in lab neurons without the bell-shaped drop-off and overexcitation that stronger AMPA potentiators tend to cause [1]. It has only been studied in cells and animals, so it remains an experimental research compound rather than an established nootropic.
Lisdexamfetamine is a central nervous system stimulant used to treat attention-deficit hyperactivity disorder (ADHD) and moderate-to-severe binge eating disorder. It is a prodrug of dextroamphetamine, meaning it is inactive until the body converts it into the active stimulant, which gives it a smooth, long-lasting effect. Sold mainly under the brand name Vyvanse, it is a once-daily oral medicine and a controlled substance.
Methylphenidate is a central nervous system stimulant widely used to treat attention-deficit hyperactivity disorder (ADHD) and narcolepsy. Sold under brand names such as Ritalin and Concerta, it works by blocking the reuptake of the neurotransmitters dopamine and norepinephrine, raising their levels in the brain and improving attention and impulse control. First synthesized in the 1940s, it is one of the most commonly prescribed medications for ADHD and is a controlled substance because of its potential for misuse.
Serdexmethylphenidate is a prodrug of the stimulant dexmethylphenidate, created by attaching the amino acid serine to the active drug so that it is only slowly converted to its active form in the gastrointestinal tract. It is used to treat attention-deficit/hyperactivity disorder (ADHD) and is marketed in the United States as part of the combination capsule Azstarys, which pairs it with a small amount of immediate-release dexmethylphenidate. The prodrug design gives a rapid onset with an extended duration of effect and is intended to reduce the potential for misuse.
Viloxazine, sold as extended-release Qelbree, is a non-stimulant ADHD medication approved for children, adolescents, and adults. It works mainly as a norepinephrine reuptake inhibitor with additional serotonergic modulation and is not a controlled substance; however, it carries an FDA boxed warning for suicidal thoughts and behaviors and is a strong CYP1A2 inhibitor with important drug interactions.
A laboratory reference agonist, not a drug. SKF 81297 is the tool compound researchers reach for when they want to switch on D1-like receptors fully and selectively, and it has never been given to a human [22].
24(S)-Hydroxycholesterol (historically named cerebrosterol) is an endogenous oxysterol (an oxygenated derivative of cholesterol) generated almost exclusively in neurons by the enzyme cholesterol 24-hydroxylase (CYP46A1). It is the principal chemical route by which the brain, which cannot degrade cholesterol, exports its surplus; because the added hydroxyl group at carbon 24 allows the molecule to cross the blood-brain barrier (the selective interface between blood and brain tissue), plasma levels of 24(S)-hydroxycholesterol serve as an accessible marker of brain cholesterol turnover and neuronal mass. Beyond its housekeeping role, it is a bona fide neurosteroid; at physiological concentrations it acts as a potent positive allosteric modulator of N-methyl-D-aspartate (NMDA) receptors (a class of glutamate-gated ion channels central to learning and memory) and as an agonist of liver X receptors (LXR, nuclear receptors that govern lipid handling). Its pharmacology inspired the synthetic analog dalzanemdor (SAGE-718), an NMDA receptor positive allosteric modulator developed for cognitive impairment.
3α-Androstanediol (5α-androstane-3α,17β-diol) is an endogenous neurosteroid formed as the terminal 3α-reduced metabolite of dihydrotestosterone (DHT, the most potent natural androgen). Despite its androgenic origin it binds the androgen receptor only weakly; its defining pharmacology is potent positive allosteric modulation of the GABA-A receptor (the brain's principal inhibitory chloride ion channel), which produces anxiolytic (anxiety-reducing) and anticonvulsant (seizure-suppressing) effects in animal models. It is widely regarded as the androgenic counterpart of allopregnanolone (the analogous progesterone-derived neurosteroid), and is proposed to mediate much of the influence that testosterone exerts on seizure threshold, anxiety, and mood in males. It additionally acts as a ligand of estrogen receptor beta (ERβ), which may underlie some of its cognitive and neuroprotective actions.
522-054 is a laboratory research compound built in Kelvin Gee's group at the University of California, Irvine to do two opposite things to the hippocampus at once: strengthen α7 nicotinic acetylcholine receptors and block the α5-subunit-containing GABA-A receptors that hold pyramidal cells under constant inhibition. In rats the combination potentiated synapses, lowered the threshold for long-term potentiation, and restored learning and attention that had been disrupted either by scopolamine or by a traumatic brain injury months earlier. The whole published record is two primary papers, both in rats and rat tissue, plus one review that summarises them. No human has been given it and no clinical trial exists.
7,8,3'-Trihydroxyflavone is a close relative of 7,8-dihydroxyflavone with one extra hydroxyl, reported in the founding work on that compound to produce an even stronger effect on TrkB signalling. ⚠️ It has no measured binding affinity at TrkB. No Ki, Kd, IC50 or EC50 from a binding assay has ever been published for it, and the potency figures that circulate are fold-changes in signalling readouts, which are not measurements of target engagement. ⚠️ It was one of the compounds tested directly in an independent replication attempt, and it was inactive.
Amyloid beta (Aβ), historically called the A4 peptide, is a short peptide of roughly 36 to 43 amino acids best known as the principal constituent of the amyloid plaques found in the brains of people with Alzheimer's disease. It is produced naturally in the body through enzymatic cleavage of a larger membrane protein, and its accumulation and aggregation are central to the leading theory of how Alzheimer's disease develops.
ABT-089, also known as pozanicline, is a synthetic small molecule that acts as a partial agonist at neuronal nicotinic acetylcholine receptors, with selectivity for the α4β2 subtype. Developed by Abbott Laboratories, it was investigated as a cognitive enhancer and as a candidate treatment for attention-deficit/hyperactivity disorder (ADHD) and other cognitive conditions.
ABT-126 was AbbVie's (formerly Abbott's) selective alpha7 nicotinic acetylcholine receptor agonist, developed for both cognitive impairment in schizophrenia and Alzheimer's disease. The alpha7 receptor is heavily expressed on hippocampal and prefrontal circuits involved in learning and attention, and it was a hot target through the 2010s after epidemiological observations tied smoking to modest cognitive benefits in schizophrenia patients. A Phase 2 trial found a real procognitive signal, but only in nonsmokers; smokers, whose alpha7 receptors were presumably already saturated or desensitized by nicotine, showed nothing. A larger Phase 2b confirmatory trial in nonsmokers, and a separate one in smokers, both failed to show meaningful benefit, and AbbVie discontinued the program around 2016 along with much of the industry's broader retreat from alpha7 agonists.
Abbott Laboratories built ABT-239 as a drug-like, orally active histamine H3 antagonist with real human-development ambitions behind it, unlike most H3 tool compounds; it was investigated as a candidate for ADHD, Alzheimer's disease, and schizophrenia-related cognitive deficits. It bound the human H3 receptor with subnanomolar potency and more than 1000-fold selectivity over the other histamine receptor subtypes, and it worked in rodent cognition and stress models. Abbott dropped it from human trials after it showed QT interval prolongation, a cardiac liability serious enough to end clinical plans outright, and ABT-239 has since lived on purely as a widely used preclinical benchmark for newer H3 antagonists.
AC-260584 is an Abbott Laboratories research compound from the 2000s, part of the same M1-muscarinic-agonist wave as sabcomeline and xanomeline but never carried past the tool-compound stage. It was designed as an orally bioavailable, functionally selective M1 agonist that improved cognitive performance in animal testing while sidestepping the receptor subtypes responsible for the GI and cardiac side effects that plagued earlier muscarinic drugs. Unlike some of its contemporaries, AC-260584 does not appear to have been pushed into human trials; its public record is essentially one core pharmacology paper, making it a compound that lives almost entirely in the preclinical literature.
ACD856 is an experimental drug from the Swedish company AlzeCure Pharma designed to make the brain's own growth factors work harder rather than replacing them; it attaches to the Trk receptors that BDNF and NGF normally act through and amplifies their signal. In animals it improved memory and produced antidepressant-like effects, and in healthy volunteers it was well absorbed, reached the brain, and caused few side effects at single doses up to 150 mg. The evidence stops there; ACD856 has never been tested for effectiveness in anyone with Alzheimer's disease or any other condition, and every published study on it was written by employees of the company that owns it. It is not approved as a medicine anywhere and is currently sold only as a laboratory chemical labelled not for human use.
Adafenoxate is a little-known nootropic that is essentially the adamantane version of meclofenoxate (centrophenoxine). Like its parent it pairs an ester carrier with DMAE (dimethylaminoethanol), a choline-related molecule tied to acetylcholine and to membrane maintenance, but swaps the parent's chlorophenoxyacetic acid for a bulky adamantane group. Almost all of what is known comes from a cluster of Bulgarian rodent studies from the late 1980s and early 1990s, where it behaved like a cholinergic, monoamine-modulating, memory-protective agent. There is essentially no modern or human data, so it is a research curiosity rather than an established supplement.
Adamantyl carbonyl proline is an obscure synthetic compound that links a rigid adamantane cage to the amino acid proline through a carbonyl, or amide, bond. It has circulated in nootropic circles as a putative cognitive enhancer, but it is essentially uncharacterized in the peer-reviewed literature, with no published human trials. Much of what is claimed about it is inferred from the general chemistry of adamantane-containing drugs and from unrelated proline-based peptides rather than from direct study of the molecule itself.
Adapromine is a Soviet-era aminoadamantane, a close relative of amantadine and rimantadine that carries a longer (propyl) side chain. Like the rest of the family it was used as an anti-influenza agent that blocks the viral M2 proton channel, but Russian pharmacology attributed to it extra antiparkinsonian and mild psychostimulant/antidepressant-like activity. The best-characterized data are Russian EEG studies showing cortical activation consistent with a catecholaminergic, stimulant-leaning profile. It is obscure outside the Russian literature and has essentially no modern human trial data.
Allithiamine is a naturally occurring, fat-soluble derivative of thiamine (vitamin B1) that was first discovered in garlic in the 1950s. It forms when a compound from crushed garlic reacts with thiamine, producing an open-ring thiamine disulfide that the body can absorb more readily than ordinary thiamine. It is the original member of a family of lipophilic thiamine derivatives, which also includes sulbutiamine and fursultiamine, developed to raise vitamin B1 levels more effectively than the standard vitamin.
Aloracetam is an experimental nootropic compound that was investigated as a potential treatment for cognitive impairment, most notably Alzheimer's disease. It is often grouped with the racetam family of cognition agents, though its structure departs from the classic 2-pyrrolidinone racetams. The compound was never brought to market and holds no regulatory approval in any major jurisdiction [1][2].
alpha-conotoxin mii is a cone-snail peptide toxin and the foundational research probe for alpha6-containing nicotinic receptors; native mii blocks both alpha3beta2 and alpha6* subtypes, but engineered analogs (mii[h9a;l15a], mii[s4a,e11a,l15a]) reach ~590-1000-fold alpha6 selectivity at low-nanomolar potency; a lab tool, not a drug, but the one that unlocked alpha6* dopamine-terminal pharmacology.
alpha-conotoxin pia is a cone-snail (conus purpurascens) peptide toxin and the first ligand able to cleanly discriminate alpha6- from alpha3-containing nicotinic receptors; a highly alpha6beta2*-selective research probe that sharpened the interpretation of 'mii-sensitive' dopamine and gaba experiments; a lab reagent, not a drug.
alpha-conotoxin txib is a conus textile peptide toxin and one of the most selective alpha6/alpha3beta2beta3 nicotinic antagonists known (rat ic50 ~28 nm, sparing other rat subtypes), with a human alpha6/alpha3beta4 off-target as a species-difference caveat; a clean research probe and drug-design lead for addiction and parkinson's, not a therapeutic in itself.
Alpha-pinene is a bicyclic monoterpene and one of the most widely distributed terpene compounds in nature. It is a principal constituent of the resin and essential oils of conifers such as pine and spruce and is also present in rosemary, many culinary herbs, and cannabis, lending these plants their characteristic fresh, piney aroma. Alongside its role as a fragrance material and industrial feedstock, alpha-pinene has been studied for a range of biological activities, including anti-inflammatory, antimicrobial, and nervous-system effects [1][2].
Alvameline was Lundbeck's attempt at a smarter cholinergic drug for Alzheimer's disease. Rather than pushing every muscarinic receptor at once, the way older agonists did, it was built to be a partial agonist at M1, the postsynaptic receptor thought to carry the cholinergic signal for memory, while blocking M2 and M3, the receptors behind the presynaptic brake and behind most of the salivation, sweating and gut cramping that had sunk earlier compounds. In animals the design held up: it produced none of the tremor, hypothermia or drooling that non-selective agonists cause in mice, and it read as its own thing in drug discrimination rather than as a copy of either a full agonist or a cholinesterase inhibitor. The clinic went the other way. A six-month trial across 29 centres randomised 496 people with probable Alzheimer's disease to placebo or 25, 50 or 100 mg three times daily and found nothing on either primary endpoint; among completers the highest dose actually trended worse, and side effects still climbed with dose. Development stopped. The molecule had a brief second life as a candidate bladder antimuscarinic, where the M3 blockade was the point rather than a design compromise, and nothing came of that either.
AMN082 is the first identified selective allosteric agonist of the mGlu7 receptor, a group III metabotropic glutamate receptor that is the most abundant and evolutionarily conserved of the family and is concentrated at presynaptic terminals. It became the primary pharmacological tool for probing mGlu7 function in stress, anxiety, fear, addiction and depression. Because mGlu7 sits at active synaptic zones and requires high glutamate concentrations for physiological activation, an allosteric agonist offered a unique way to engage it directly. AMN082 is significant as the compound that opened experimental access to mGlu7 pharmacology, though its off-target effects require careful interpretation.
Amycenone is a standardized bioactive extract obtained from the Yamabushitake mushroom (Hericium erinaceus), studied as an anti-inflammatory antidepressant. In a lipopolysaccharide-induced mouse model of inflammatory depression, oral amycenone blocked the rise in tumor necrosis factor-alpha, increased the anti-inflammatory cytokine interleukin-10, and reduced depression-like immobility in the tail-suspension and forced-swim tests, with effects comparable to the SSRI paroxetine. It is investigated as a natural supplement for inflammation-related mood disorders.
Apoaequorin is the protein component of aequorin, a calcium-sensitive, light-emitting protein originally isolated from the jellyfish Aequorea victoria. In the laboratory it is widely used as a tool for detecting calcium inside cells. It is also the active ingredient in the marketed memory supplement Prevagen, a use for which independent reviewers have found the supporting evidence weak, and which drew a false-advertising action from United States regulators.
AQW051 was Novartis's alpha7 nicotinic acetylcholine receptor partial agonist, developed alongside ABT-126, TC-5619, and encenicline in the industry-wide push to translate the alpha7 receptor's role in hippocampal and prefrontal circuits into a working schizophrenia cognition drug. Novartis took an unusually mechanistic approach to testing it, using functional MRI in a randomized crossover trial to watch how the drug changed brain activation during working-memory and episodic-memory tasks in people with chronic, stable schizophrenia, rather than relying on behavioral scores alone. The imaging trial found AQW051 did alter neuronal activity in prefrontal and hippocampal regions, but it did not translate into a consistent cognitive benefit, and in smokers at higher doses working memory performance seemed to get worse rather than better. Combined with the broader wave of alpha7 agonist failures across the industry, Novartis did not carry AQW051 forward into larger confirmatory trials.
Arecaidine is the carboxylic acid sitting one hydrolysis step away from arecoline, the alkaloid that makes areca nut a stimulant. Lime in a betel quid strips the methyl ester off arecoline, and the body does the same thing afterwards, so anyone chewing areca is exposed to substantial arecaidine whether or not it was in the nut to begin with. Chemically it is N-methylguvacine, which puts it in the same small family as guvacine and nipecotic acid, and that family does one interesting thing: it blocks GABA reuptake. Johnston's group reported that in Nature in 1975, and a follow-up in cat spinal cord and cerebellum confirmed that locally applied arecaidine makes GABA's inhibitory effect last longer without touching glycine. The catch is what happened when the same group gave it intravenously. Nothing. Systemic arecaidine failed to alter GABA-mediated synaptic inhibition at all, and a full gram per kilogram under the skin only marginally blunted bicuculline lethality in mice, with little or no anticonvulsant effect to speak of. It is a real transporter inhibitor that cannot reliably get where it would need to act, which is why it stayed a laboratory tool rather than becoming a drug.
Arecoline is the main alkaloid of the areca nut and a partial agonist at both muscarinic and nicotinic acetylcholine receptors; it is the pharmacologically active core of betel quid chewing rather than a therapeutic agent.
ASP-4345 is an investigational small molecule developed by Astellas Pharma that acts as a positive allosteric modulator of the dopamine D1 receptor, amplifying signaling only where and when endogenous dopamine is released rather than directly activating the receptor. This mechanism is of interest because D1 transmission in the prefrontal cortex is central to working memory and executive function, and class agents such as DETQ enhance cortical and hippocampal acetylcholine efflux and reverse memory deficits in animal models. ASP-4345 was advanced as an add-on therapy for cognitive impairment associated with schizophrenia, a core feature of the disorder for which no treatment is approved, and completed Phase 1 single and multiple ascending-dose pharmacokinetic and pharmacodynamic studies. Compound-specific clinical data remain limited, so much of its rationale draws on the broader D1 positive allosteric modulator literature.
ASP2905 is an experimental small molecule that acts as a potent and selective inhibitor of the voltage-gated potassium channel Kv12.2, encoded by the KCNH3 (BEC1) gene and enriched in the hippocampus and cerebral cortex. Kv12.2 sits near the neuronal resting potential and restrains firing threshold, so blocking it raises excitability in principal neurons; genetic disruption of the same channel enhances performance on learning and memory tasks in mice. Developed by Astellas Pharma, ASP2905 was investigated preclinically as a cognitive enhancer and for the cognitive and behavioral symptoms of schizophrenia, and it has demonstrated psychoactivity in rodent models. Direct published characterization of the compound itself remains limited, so much of its rationale rests on the well described biology of its molecular target.
AVL-3288 (also known as UCI-4083) is an experimental compound that acts as a type I positive allosteric modulator of the α7 nicotinic acetylcholine receptor. Rather than activating the receptor directly, it strengthens the receptor's response to the brain's own acetylcholine, and it has been investigated as a way to improve cognition, particularly in schizophrenia.
AVN-322 is an investigational, highly selective 5-HT6 serotonin receptor antagonist developed by Avineuro Pharmaceuticals as a potential cognitive-enhancing treatment for Alzheimer's disease.
AWD 52-39 is an investigational lysergamide (a chemical relative of LSD) that was developed as a nootropic for cognitive disorders before its discontinuation.
Basimglurant (developmental codes RG7090 and RO4917523) is a potent, selective negative allosteric modulator of the mGlu5 receptor developed by Roche as a once-daily modified-release medicine for psychiatric disorders. It was advanced principally as an adjunctive treatment for major depressive disorder and for fragile X syndrome, based on preclinical evidence that mGlu5 blockade produces broad anxiolytic and antidepressant-like effects. A phase 2b depression trial missed its clinician-rated primary endpoint but showed consistent improvement on patient-rated measures, while a fragile X trial did not meet its primary behavioural outcome. Basimglurant is notable for its favourable drug-metabolism profile and its position as one of the most clinically advanced mGlu5 negative allosteric modulators.
Bavisant started life at Johnson & Johnson as JNJ-31001074, a potent, brain-penetrant histamine H3 antagonist aimed at adult ADHD; a controlled dose-ranging trial found it did not produce a clinically meaningful benefit over placebo, and J&J's ADHD program quietly closed. The molecule's story did not end there. BenevolentAI, an AI-driven drug discovery company, later licensed the same compound, renamed it bavisant, and repositioned it around a side effect noted in the original data, dose-dependent insomnia, betting that the same wake-promoting H3 blockade could help excessive daytime sleepiness in Parkinson's disease instead. That reran the drug through a Phase IIb trial testing three doses against placebo in roughly 230 Parkinson's patients, an unusually direct case of an abandoned CNS candidate getting a second clinical life through indication-hopping rather than fresh chemistry.
Besipirdine was Hoechst-Roussel's attempt to broaden the cholinergic-hypothesis playbook for Alzheimer's disease by hitting two neurotransmitter systems at once, enhancing both cholinergic and noradrenergic transmission rather than acetylcholine alone, on the theory that a dual mechanism might outperform pure cholinesterase inhibitors. In a 275-patient trial, patients on besipirdine held steady on cognitive testing over three months while the placebo group declined, a genuinely encouraging signal for a still-experimental Alzheimer's drug in the mid-1990s. That promise collapsed in Phase III, where a subset of patients developed serious cardiovascular side effects, forcing Hoechst-Roussel to abandon the program; the company had also explored besipirdine for other indications, including multiple sclerosis-related walking impairment, but none of it reached market.
Bifemelane (brand names Alnert and Celeport; development code MCI-2016) is a Japanese cerebral activator and antidepressant that acted mainly as a reversible, competitive inhibitor of monoamine oxidase type A, with weaker noncompetitive inhibition of MAO-B [1]. It was prescribed in Japan from the late 1980s for the emotional and cognitive disturbances that follow cerebral infarction [6], and was also trialed in glaucoma [9]. Most of its evidence comes from small Japanese studies from the 1980s and 1990s; it was pulled from the market in 1998 after a national re-evaluation judged the effectiveness of that whole class of cerebral metabolic enhancers to be unproven.
Bilobalide is a sesquiterpene trilactone, a plant compound found almost exclusively in the leaves of the ginkgo tree (Ginkgo biloba). It is one of the characteristic terpene trilactones that, together with the ginkgolides, define standardized ginkgo extracts [1]. In laboratory research it has drawn attention as a neuroprotective agent and as a negative modulator of GABA-A receptors, though its full range of actions in the brain is not completely understood [3][4]. It reaches people mainly as a minor constituent of ginkgo leaf supplements rather than as an isolated product.
Biochanin A is a naturally occurring isoflavone, an O-methylated member of the flavonoid family that is classified as a phytoestrogen. It is found in red clover, soy, chickpeas, alfalfa, peanuts, and other legumes, and in the body it can be converted into the better-known isoflavone genistein [1]. It has been investigated for a wide range of biological activities, including weak estrogen-like effects, inhibition of the endocannabinoid-degrading enzyme FAAH, and anti-inflammatory actions, largely in laboratory and animal studies [3][4]. It reaches people mainly through legume-rich diets and red clover supplements rather than as an isolated drug.
BnH-015B is an oral compound from a Korean company, in a first-in-human trial for Alzheimer's disease. It is described by its sponsor as a positive modulator at the GluN2B site of the NMDA receptor. ⚠️ Nothing about it has ever been published. There is no structure, no CAS number, no chemistry record, no potency measurement, no pharmacokinetic data and no preclinical paper in the public record. This entry exists to say what is and is not known, because the compound appears in drug-pipeline listings in a form that reads like established pharmacology.
Brivaracetam is a racetam-derivative antiseizure medication and an analog of levetiracetam, used as add-on therapy for focal, or partial-onset, seizures in people with epilepsy. It was rationally designed as a high-affinity, highly selective ligand of the synaptic vesicle glycoprotein SV2A, binding the target roughly 15 to 30 times more tightly than levetiracetam, and is associated in clinical use with a more favorable behavioral and psychiatric tolerability profile. Developed by the company UCB and marketed as Briviact, it received European and United States approval in 2016.
A non-selective cholinergic agonist that acetylcholinesterase cannot readily break down; in United States practice it survives as an ophthalmic drug, and in the laboratory as one of the most heavily used tools in cholinergic pharmacology.
CE-158 is an investigational, highly selective atypical dopamine transporter inhibitor developed by academic groups in Vienna, Salzburg, and Cagliari as a modafinil-derived cognitive enhancer. In rodents it raises prefrontal and hippocampal dopamine, restores age-related synaptic and cognitive decline, and improves behavioral flexibility without signs of abuse liability. It is a preclinical research compound with no human data.
Cebaracetam is an experimental nootropic drug of the racetam family that was studied during the 1990s as a candidate treatment for cognitive and memory disorders [1]. In chemical terms it is a chlorinated, piperazinone-bearing analogue of phenylpiracetam, with the molecular formula C16H18ClN3O3 [2]. The compound advanced into phase II clinical trials, but its development was discontinued in 1995 and it was never marketed [1]. Its mechanism of action was never clearly defined.
Celastrus paniculatus is a woody climbing shrub of the family Celastraceae, native to India and known in English as the intellect tree or black oil plant [1][2]. Its seeds and the oil pressed from them have a long history in Ayurvedic, Unani, and Siddha traditional medicine, where they are counted among the memory-supporting 'Medhya Rasayana' tonics and used for a range of nervous-system complaints [2][3]. Modern laboratory and animal studies have examined the seed oil and extracts for antioxidant, neuroprotective, and nootropic activity, though controlled human trials are lacking [2][4].
A once-daily reuptake inhibitor of norepinephrine, dopamine and serotonin, approved July 2026 for ADHD in adults and children aged 6 and older.
Cerebroprotein hydrolysate is a mixture of low-molecular-weight peptides and free amino acids extracted from porcine brain tissue and used as a neuroprotective preparation, chiefly for cognitive impairment and dementia [2][4]. It is closely related to Cerebrolysin, a similarly prepared brain peptide product, and is marketed mainly in China and other parts of Asia rather than in Western countries [1][3]. Laboratory and animal studies attribute neurotrophic and antioxidant actions to the preparation, though rigorous human evidence remains limited [2][4].
Cerlapirdine was Pfizer's 2010s-era entry into the crowded field of 5-HT6 receptor antagonists chasing Alzheimer's disease, following the same mechanistic bet as idalopirdine and intepirdine: blocking 5-HT6 was thought to indirectly boost cortical acetylcholine and glutamate release and improve cognition. Pfizer ran a Phase II trial specifically in mild-to-moderate Alzheimer's patients who had existing neuropsychiatric symptoms while already stable on donepezil, a narrower bet aimed at the behavioral side of dementia rather than memory alone. The trial, published in 2018, did not separate cerlapirdine from placebo, closing out Pfizer's 5-HT6 program alongside the broader failure of the entire drug class across multiple companies in the same period.
An oral muscarinic agonist approved in the United States in 2000 for the symptoms of dry mouth in Sjogren's syndrome, where it drives whatever secretory tissue the disease has left.
CF3CN is a laboratory code for an optimised replacement for 7,8-dihydroxyflavone, redesigned to resist the metabolism that destroys the parent compound and to reach the brain better. Its catechol ring is swapped for a fused imidazole carrying a trifluoromethyl group, and a nitrile replaces the electron-donating group on the other ring. ⚠️ It is the one compound in this family with a real binding measurement. Surface plasmon resonance gave a dissociation constant of 80.2 nanomolar against the TrkB extracellular domain, measured alongside 7,8-dihydroxyflavone at 184.5 nanomolar in the same experiment. ⚠️ It also has no public registry identity at all: no CAS number, no PubChem record, no ChEMBL entry.
Ciproxifan never had a pharma sponsor chasing an indication; it exists almost entirely as an academic tool compound, and it became the reference histamine H3 antagonist that an entire generation of sleep, attention, and Alzheimer's-related rodent studies were built around. Its defining quirk is species selectivity: it binds rodent H3 receptors in the subnanomolar range but only moderately at the human receptor, which is exactly why it stayed a lab reagent instead of becoming a clinical candidate. Later work found it also reversibly inhibits monoamine oxidase A and B, an unplanned second mechanism that complicates interpreting some of the older behavioral data attributed purely to H3 blockade.
Clitoria ternatea is a perennial climbing legume of the family Fabaceae, widely known as butterfly pea or blue pea for its vivid blue flowers [1][5]. Native to equatorial Asia, it is now grown across the tropics as an ornamental, a nitrogen-fixing cover crop, and a source of natural blue food colouring [1][5]. In the traditional medicine of South Asia it has long been used as a memory tonic, and modern laboratory studies have examined its extracts for effects on cognition and the nervous system [2][6].
Cocoa flavanols are a group of plant compounds of the flavanol (flavan-3-ol) family, a subclass of flavonoids, found naturally in the beans of the cacao tree [1][2]. The main members are epicatechin and catechin together with their larger cousins the procyanidins, and they are responsible for much of the interest in the possible heart and circulation benefits of cocoa and dark chocolate [1][2]. Research has linked flavanol-rich cocoa to small reductions in blood pressure and to improved function of the blood vessel lining, though the amounts present in ordinary chocolate are modest and are cut down by common processing steps [2][3].
Colivelin is a synthetic 26-amino-acid hybrid peptide built by fusing a short activity-dependent neurotrophic factor fragment (ADNF-9, SALLRSIPA) to the N-terminus of a potent humanin derivative, AGA-(C8R)HNG17. It was engineered to protect neurons from the kinds of insults tied to Alzheimer's disease and other neurodegeneration, and it does so in cell models at femtomolar concentrations, far below its parent peptides. Researchers look at it mainly as a neuroprotective tool compound rather than an approved drug.
Conessine is a steroidal alkaloid found in the bark of tropical plants of the dogbane family (Apocynaceae), most notably Holarrhena and Funtumia species [1][4][5]. Long used in traditional medicine as a remedy for dysentery and other infections, it has drawn modern scientific interest as a naturally occurring blocker of the histamine H3 receptor in the brain [1][2]. It is not an approved medicine but is studied as a research compound and as a chemical starting point for designing new H3-targeting drugs [2][3].
Convolvulus pluricaulis is a small perennial herb of the morning glory family (Convolvulaceae), native to India and best known in Ayurvedic medicine as shankhpushpi [1][2]. It has long been used as a brain tonic to support memory and to calm the mind, and it is one of several plants traditionally sold under the shankhpushpi name [2][4]. Modern laboratory research has examined its extracts for memory-enhancing, anxiety-reducing and neuroprotective effects, although evidence in humans remains limited [2][3].
Corallocin A is an isoindolinone natural product first isolated from the coral tooth mushroom Hericium coralloides and subsequently found in Hericium erinaceus fruiting bodies. It induces both nerve growth factor and brain-derived neurotrophic factor expression in human astrocytes, making it one of the dual-neurotrophin inducers of the Hericium genus. Its ability to raise BDNF as well as NGF distinguishes it from the classic NGF-focused hericenones and links it to memory-relevant signaling.
Corallocin B is a benzofuranone natural product isolated from the mushroom Hericium coralloides alongside corallocins A and C. It induces nerve growth factor and brain-derived neurotrophic factor expression in human astrocytes and, unusually for this class, also shows antiproliferative activity against endothelial and cancer cell lines. This combination of neurotrophic and antiproliferative properties makes it a distinctive dual-activity member of the Hericium neuroactive metabolites.
Cutamesine (SA4503) is a selective agonist of the sigma-1 receptor, an endoplasmic reticulum chaperone protein that modulates calcium signaling, mitochondrial function, and multiple neurotransmitter systems. Preclinical work shows that sigma-1 activation enhances neurite and axon outgrowth, protects neurons from oxidative and excitotoxic stress, and improves functional recovery when given days after experimental ischemic stroke, acting through neuroplasticity rather than acute neuroprotection. A phase 2 clinical trial in acute ischemic stroke found cutamesine safe and well tolerated, with a post hoc signal of greater neurological improvement among more severely affected patients. The same sigma-1 mechanism has drawn interest for depression, cognitive impairment, and motor neuron disease, and the carbon-11 labeled compound has been used as a PET radiotracer to quantify sigma-1 receptor occupancy. It has reached human testing but is not an approved drug.
CX-1739 is a second-generation, low-impact ampakine developed by RespireRx Pharmaceuticals (formerly Cortex) as a positive allosteric modulator of AMPA receptors. Unlike early high-impact ampakines, it is designed to enhance excitatory transmission without producing excitotoxicity, and it crosses the blood-brain barrier rapidly. Its most striking property is the ability to reverse opioid- and sedative-induced respiratory depression without blocking analgesia, and it also improves social behavior and cognition in preclinical models. It has been examined in early human respiratory studies.
CX-516 (Ampalex) is the first-in-class ampakine, developed by Cortex Pharmaceuticals, historically important as the compound that established AMPA-receptor positive modulation as a cognition strategy. It facilitates long-term potentiation and memory in animal models, but its weak potency and short half-life undermined every human trial.
CX-546 is a benzoxazine ampakine developed by Cortex Pharmaceuticals as a positive allosteric modulator of AMPA-type glutamate receptors. It is a first-generation, high-impact ampakine that markedly slows receptor deactivation and desensitization, boosting excitatory transmission, long-term potentiation, and neurotrophin expression in the hippocampus. Widely used as a laboratory tool compound, it has illuminated how AMPA modulation drives synaptic plasticity, astrocyte energetics, and BDNF signaling. It never became a clinical product but remains an important reference ampakine.
CX-614 is a benzoxazine ampakine from the Cortex Pharmaceuticals program and a positive allosteric modulator of AMPA-type glutamate receptors. It is best known as the compound that first demonstrated ampakines can chronically elevate brain-derived neurotrophic factor without permanently down-regulating AMPA receptors, provided dosing is spaced. This made it a foundational tool for the concept of using AMPA modulators to sustain neurotrophin signaling for neuroprotection. It was never a clinical product but remains one of the most cited experimental ampakines.
CX-717 is a later, more brain-penetrant ampakine (Cortex Pharmaceuticals, later RespireRx) notable for offsetting sleep-deprivation cognitive decline in nonhuman primates and, at high dose, in humans, plus a distinct adult-ADHD development track. It has a 'low-impact' AMPA-PAM profile.
Cyclazodone is a stimulant research chemical from the oxazolidinone family; it is essentially a cyclized N-aryl relative of pemoline. People describe it as a fairly clean, focus-heavy stimulant that leans dopaminergic (acting on the brain's reward and motivation chemistry), with a slower onset and a long tail. It is unscheduled in many places and sold as a gray-market nootropic rather than an approved medicine.
Cycloprolylglycine is a small cyclic dipeptide found naturally in brain tissue, and the compound usually named as Noopept's active metabolite. It is studied under two names that describe the same molecule: Russian work calls it cycloprolylglycine, New Zealand work calls it cyclic glycine-proline. ⚠️ The active-metabolite claim is weaker than its popularity suggests. The primary source found the compound in untreated animals as well as treated ones, and reported a 2.5-fold rise at a single hour-long timepoint. The same institute later published that Noopept and this metabolite behave differently in a learning task, which is difficult to reconcile with a simple prodrug relationship.
Cytidine is a pyrimidine nucleoside made up of the base cytosine joined to a ribose sugar. It is one of the fundamental building blocks of RNA, where its phosphorylated forms act as nucleotides, and it also feeds into the synthesis of cell membrane phospholipids. In humans, dietary and supplemental cytidine is largely converted to the related nucleoside uridine, and it is closely tied to the choline donor CDP-choline (citicoline); it has additionally been studied in a small way for mood disorders.
D-Cycloserine is a small molecule that acts as a partial agonist at the glycine co-agonist site of the NMDA glutamate receptor, and it is also a genuine antibiotic (used historically against tuberculosis). Because NMDA receptors are central to learning, it has been studied as an add-on to psychotherapy to enhance cognition and, in particular, fear extinction (the process of unlearning a fear). Its interest for the brain comes from gently boosting NMDA-dependent plasticity.
D-serine is the D-enantiomer of the amino acid serine and acts as a signaling molecule in the brain, where it serves as a co-agonist at the NMDA subtype of glutamate receptor. It is produced from L-serine by the enzyme serine racemase and is one of the more abundant D-amino acids in mammals, concentrated in regions such as the forebrain. Because NMDA receptors require a co-agonist alongside glutamate in order to open, glia-derived D-serine helps govern synaptic plasticity, learning, and memory; reduced D-serine signaling is central to the NMDA-hypofunction model of schizophrenia, in which serum levels are decreased, and it has also been investigated as an adjunct in major depression and as a predictor of response to ketamine.
A dechlorinated mazindol analogue tuned to be a clean noradrenaline reuptake blocker plus a partial orexin-2 agonist; an orexin-forward wake drug aimed at narcolepsy.
Deoxygedunin is a natural product from the Indian neem tree and from andiroba seed oil, a limonoid of the gedunin family. It is sold alongside the flavone TrkB compounds and is chemically unrelated to them; it appears in that group only because it came out of the same screen. ⚠️ Its literature is remarkably small. PubMed indexes six papers containing the word at all, one of which merely identifies it as a constituent of seed oil and has nothing to do with the nervous system. There is no second independent pharmacology programme anywhere.
Docosahexaenoic acid (DHA) is a long-chain omega-3 polyunsaturated fatty acid, designated 22:6(n-3), that serves as a major structural lipid in the brain, retina, and wider nervous system. It is obtained chiefly from fatty fish, fish oil, and algae-derived oils, and the human body can form only small amounts of it from the shorter omega-3 precursor alpha-linolenic acid. DHA is widely used in dietary supplements and infant formulas and is studied for roles in neurodevelopment, cognition, and cardiovascular health.
DHEA sulfate (DHEAS) is the 3-beta sulfate ester of dehydroepiandrosterone and the most abundant circulating steroid in the human body, present in plasma at concentrations roughly a thousandfold higher than unconjugated DHEA. Synthesized principally in the zona reticularis of the adrenal cortex, it functions as a stable, long-lived reservoir that is interconverted with DHEA and supplies a precursor pool for downstream androgens and estrogens. Within the nervous system it is classified as a neurosteroid (a steroid synthesized in or acting directly upon nervous tissue); it acts as an agonist at the sigma-1 receptor (an intracellular chaperone protein), a positive modulator of the NMDA receptor (a glutamate-gated excitatory ion channel), and a negative allosteric modulator of the GABA-A receptor (the brain's principal inhibitory ion channel), giving it a net excitatory, pro-cognitive neuromodulatory profile. Circulating concentrations fall markedly with age, a decline termed adrenopause that has made DHEAS a widely studied biomarker of adrenal function, cognitive aging, and longevity.
Dihydrexidine (DAR-0100) is a synthetic phenanthridine and the first full agonist at the dopamine D1 receptor, developed largely through the work of David Nichols and Richard Mailman. Because prefrontal D1 signaling is central to working memory, it has been investigated as a cognitive enhancer, particularly for the cognitive deficits of schizophrenia and Parkinson's disease. Single low doses proved safe and tolerable in patients, but its very short duration and poor oral bioavailability limited efficacy. It remains a landmark pharmacological tool for the D1 system.
Dimiracetam is a synthetic bicyclic compound of the racetam family, related to the nootropic drug piracetam. It was originally developed as a cognition enhancer but has attracted most of its research attention as a candidate treatment for neuropathic pain, showing broad and long-lasting activity in animal models of several nerve-pain conditions, including pain caused by chemotherapy; this activity is attributed to reduced release of the excitatory neurotransmitter glutamate. It remains an investigational agent and is not an approved medicine.
Dipraglurant (developmental code ADX48621) is an orally active negative allosteric modulator of the mGlu5 receptor developed by Addex Therapeutics, chemically an imidazo-pyridine distinct from the pyridine-based mGlu5 modulators. It was studied primarily for levodopa-induced dyskinesia in Parkinson's disease, where a randomized safety trial showed good tolerability and exploratory reductions in dyskinesia. Preclinical work also demonstrated activity across models of anxiety, depression and compulsive behaviour, suggesting potential relevance to the non-motor symptoms that burden Parkinson's patients. Dipraglurant is notable as a rapidly absorbed, brain-penetrant mGlu5 negative allosteric modulator with a broad behavioural profile.
Doliracetam is an obscure synthetic compound of the racetam family, a group of acetamide-based substances studied for possible effects on cognition. Unlike the classic racetams built on a pyrrolidinone ring, it is chemically an oxindole derivative carrying an acetamide group. It was patented by the German pharmaceutical company Hoechst in the early 1980s as one of a series of compounds described as having neuroanabolic properties. Doliracetam never became an established medicine, and very little published research on it exists.
Dopamantine is an obscure dopamine prodrug: dopamine linked through an amide bond to a lipophilic adamantane (fat-soluble cage) group. The idea behind such molecules is to mask dopamine, which on its own cannot cross the blood-brain barrier, and let the body cleave off the carrier to release dopamine inside the brain for Parkinson's disease. Dopamantine itself has essentially no published pharmacology or clinical data; it is best understood as one entry in the broad, still-experimental class of dopamine and levodopa prodrugs.
Dupracetam is an experimental nootropic of the racetam (pyrrolidinone) family, structurally related to piracetam. It was investigated in the late twentieth century for possible effects on learning and cognition, yet it was never developed into an approved medicine and remains an obscure research compound with only a sparse scientific literature.
E-6801 is a potent serotonin 5-HT6 receptor agonist, characterized as a high-efficacy partial-to-full agonist depending on assay conditions, developed at Laboratorios Dr. Esteve. It is an imidazothiazole sulfonamide with very high potency at the receptor and has been used to demonstrate that 5-HT6 activation, not only blockade, can be pro-cognitive. Together with its analogue E-6837 it helped clarify how forskolin stimulation and constitutively active receptors reveal true agonist efficacy at 5-HT6. It is a research compound with no clinical development but is an influential probe of 5-HT6 agonist biology.
Ecklonia cava is an edible brown alga (seaweed) found in the coastal waters of East Asia, especially around Korea and Japan. It is a rich source of polyphenols called phlorotannins, including the marker compound dieckol, which have been studied for antioxidant, anti-inflammatory, and other biological activities. Extracts of the seaweed are used in foods, dietary supplements, and cosmetics.
Eglumegad (developmental code LY354740) is a potent, selective orthosteric agonist of group II metabotropic glutamate receptors (mGlu2 and mGlu3) developed by Eli Lilly as a novel anxiolytic. By activating presynaptic autoreceptors that restrain glutamate release, it produced robust anti-anxiety effects in animal models and, through its prodrug LY544344, showed efficacy in human generalized anxiety disorder and experimental panic. Development was halted after preclinical convulsion findings, but eglumegad remains a foundational tool compound for group II metabotropic glutamate pharmacology. It is historically important as one of the first metabotropic glutamate agonists to reach human anxiety trials.
Elunetirom (ABX-002) is an investigational thyromimetic prodrug designed to deliver selective thyroid hormone receptor beta (TR-beta) activation preferentially to the central nervous system while limiting the systemic thyroid effects that make native thyroid hormone unsuitable as a drug. It belongs to the same CNS-penetrating prodrug class as sobetirome and its amide prodrug Sob-AM2, for which preclinical studies have shown brain-targeted TR-beta engagement that stimulates oligodendrocyte differentiation, promotes myelin repair, and lowers very long chain fatty acids in models of demyelination and X-linked adrenoleukodystrophy. By recreating thyroid hormone action in the brain without body-wide hyperthyroidism, such agents are being explored as add-on treatments for mood disorders and neurological disease. As of the mid-2020s elunetirom remained in clinical trials and had not been approved for any use.
Emapunil (developmental codes XBD-173 and AC-5216) is an investigational anxiolytic that acts as a selective, high-affinity agonist of the 18-kDa translocator protein (TSPO), a mitochondrial cholesterol-transport protein once known as the peripheral or mitochondrial benzodiazepine receptor. Rather than binding the central benzodiazepine site itself, emapunil stimulates the brain's own synthesis of neurosteroids, most notably allopregnanolone, which then potentiate GABA-A receptors (the brain's main inhibitory chloride channels) to produce anxiolysis. In a landmark 2009 human panic-provocation study it reduced induced anxiety without the sedation, tolerance, or withdrawal that characterise benzodiazepines. It reached Phase 2 clinical evaluation before development was discontinued, and it remains a widely cited proof of concept for neurosteroid-based anxiolysis.
EMD-386088 is a selective serotonin 5-HT6 receptor agonist, described in some assays as a partial agonist, that is used as a pharmacological tool to study the receptor's role in mood, anxiety and cognition. It is a tetrahydropyridinyl indole developed by Merck (EMD) and is one of the more widely used 5-HT6 agonists in behavioural neuroscience. In rodent studies it produces antidepressant-like and anxiolytic-like effects after both local hippocampal and systemic administration, with effects blocked by selective 5-HT6 antagonists, confirming target specificity. It has no clinical development but is a valuable probe of 5-HT6 agonist biology.
A selective M4 positive allosteric modulator built at Pfizer and carried into schizophrenia trials by Cerevel and then AbbVie, whose phase 2 programme failed to beat placebo in November 2024.
Encenicline (EVP-6124) is an investigational, orally active, selective partial agonist of the alpha7 nicotinic acetylcholine receptor developed for cognitive impairment in schizophrenia and Alzheimer disease. Late-stage clinical development was halted after serious gastrointestinal adverse events, and it is not approved for any use.
Epiandrosterone (3β-hydroxy-5α-androstan-17-one; also called isoandrosterone) is an endogenous 5-alpha-reduced steroid formed from dehydroepiandrosterone (DHEA) and androstenedione, and it is the 3-beta-hydroxyl epimer of androsterone. It circulates in humans predominantly as its sulfate ester and functions as a weak neurosteroid (a steroid that acts on neuronal receptors rather than classical nuclear hormone receptors), producing only mild modulation of the GABA-A receptor (the brain's principal inhibitory chloride ion channel) while inhibiting glycine receptors (another inhibitory ligand-gated channel concentrated in the spinal cord and brainstem). Beyond the nervous system it is a well-characterized uncompetitive inhibitor of glucose-6-phosphate dehydrogenase (G6PD, the rate-limiting enzyme of the pentose phosphate pathway) and a recognized urinary marker of 5-alpha-reductase activity. Because it can be metabolized toward dihydrotestosterone (DHT, the most potent natural androgen), it is also sold over the counter as a non-methylated androgen prohormone.
Eptastigmine was the Italian pharmaceutical company Mediolanum's long-acting redesign of physostigmine, an old carbamate cholinesterase inhibitor whose natural form works but wears off too fast to dose conveniently; adding a heptyl (seven-carbon) chain extended its duration of action enough to make once- or twice-daily dosing plausible for Alzheimer's patients. It moved through a full decade of pharmacology, toxicology, and clinical study, including efficacy trials that showed genuine cognitive benefit over placebo. Then hematology data caught up with it, reversible neutropenia and, in a subset of patients, agranulocytosis (a dangerous collapse in infection-fighting white blood cells) showed up during clinical trials at a rate high enough that regulators would not accept the risk, and the program was discontinued despite a decade of otherwise promising work.
Erinacine A is the flagship cyathane diterpenoid produced by the mycelium of the culinary-medicinal mushroom Hericium erinaceus (Lion's Mane). It is the single most pharmacologically characterized Lion's Mane metabolite in the central nervous system, acting as a potent low-molecular-weight inducer of nerve growth factor (NGF) synthesis. Unlike the larger hericenones of the fruiting body, erinacine A is small and lipophilic enough to cross the blood brain barrier, giving it central activity after oral dosing in rodents. Preclinical work reports benefit across Alzheimer-type pathology, Parkinsonian models, ischemic stroke, metabolic-driven cognitive decline, and colorectal cancer models.
Erinacine C is a cyathane diterpenoid from Hericium erinaceus mycelium and one of the more potent members of the erinacine series for inducing nerve growth factor synthesis. Beyond neurotrophic activity, it is distinguished by a well-characterized anti-neuroinflammatory profile: in microglial models it suppresses nitric oxide and pro-inflammatory cytokine production while activating the cytoprotective Nrf2/HO-1 pathway. It is investigated as a natural neuroprotective lead for conditions driven by microglial activation and oxidative stress.
Erinacine P is a cyathane diterpenoid isolated from liquid cultures of Hericium erinaceus and is best understood as a biosynthetic precursor within the erinacine pathway that leads to erinacine A and erinacine C. Despite its precursor role it is itself neuroactive, promoting neurite outgrowth in PC12 cells at low micromolar concentrations. It is of particular interest to metabolic engineers seeking to raise erinacine A yields, since the pathway flows through erinacine P.
Etazolate (EHT-0202) is a fascinating triple-mechanism molecule: a 1970s pyrazolopyridine anxiolytic that ExonHit repurposed for Alzheimer's disease. In one compound it combines PDE4 inhibition, positive allosteric modulation of GABA-A receptors, and stimulation of alpha-secretase, which raises the neurotrophic, neuroprotective fragment sAPPalpha and steers amyloid precursor protein away from toxic amyloid. It is one of the few compounds in this class to have actually completed a placebo-controlled Phase 2 trial in Alzheimer's patients.
Etiracetam is a synthetic compound of the racetam family and a close relative of piracetam. It is a racemic mixture whose biologically active enantiomer, the S-form, is levetiracetam, a widely used antiseizure medication; investigation of levetiracetam's mechanism led to the identification of the synaptic vesicle glycoprotein SV2A as its molecular target and as a novel class of antiepileptic drug target. Etiracetam itself was investigated for effects on memory and against seizures but was not marketed, with development focusing instead on its purified active enantiomer.
Farampator (CX-691 / Org 24448) is an investigational ampakine, a positive allosteric modulator of AMPA-type glutamate receptors, advanced through the Cortex Pharmaceuticals / Organon program. It slows AMPA-receptor deactivation and desensitization to strengthen fast excitatory transmission and long-term potentiation, and in animals it raises hippocampal and prefrontal acetylcholine, prefrontal dopamine, and hippocampal BDNF mRNA. It is best known for a single, unusually instructive human trial in which one 500 mg dose improved short-term memory yet impaired episodic memory in healthy elderly volunteers.
Fencamfamine is a norbornane-derived CNS stimulant that was once marketed (as Reactivan) for fatigue, low mood, and convalescence. It works largely as an indirect dopaminergic, boosting dopamine signaling with less of the raw jolt of amphetamine. It is now a controlled or restricted substance in many countries and rarely prescribed.
Fenobam is an imidazole small molecule originally developed in the 1970s as a non-benzodiazepine anxiolytic whose mechanism was unknown until it was later identified as a selective mGlu5 negative allosteric modulator. This retrospective mechanistic discovery made fenobam an early prototype for mGlu5-based anxiolytics and a candidate for fragile X syndrome. A pilot single-dose trial in adults with fragile X syndrome reported no significant adverse effects and improvements in prepulse inhibition, a marker of sensory gating, in half of the participants. Fenobam holds historical importance as the first clinically studied mGlu5 negative allosteric modulator in humans.
Fenozolone is an oxazoline CNS stimulant closely related to pemoline and aminorex, formerly used as a mood-lifting and anti-fatigue agent. It behaves as an indirect catecholamine-releasing stimulant, increasing dopamine and norepinephrine activity. Like its chemical cousins it is now largely obsolete and controlled or unavailable in most markets.
FK-960 was Fujisawa Pharmaceutical's (Japan) 1990s answer to a completely different question than most nootropics of its era: instead of chasing acetylcholine or glutamate receptors, it tried to boost memory by stimulating somatostatin release and, downstream, glial production of GDNF (glial cell line-derived neurotrophic factor). Preclinical work showed it ameliorated memory deficits in rodent models and enhanced hippocampal signaling relevant to long-term potentiation. It moved through animal and early-stage research toward a possible Alzheimer's disease application, but somatostatin-boosting drugs never carved out a clinical niche in dementia care, and FK-960 stalled well short of approval, remembered now mostly in pharmacology reviews as a case study in an alternate route to memory enhancement.
Fluorene myristate is an obscure research compound marketed as a nootropic; based on its name and vendor descriptions it appears to be a myristic-acid ester of a fluorene or fluorenol core, likely intended as a lipophilic prodrug or slow-release form of 9-fluorenol (hydrafinil), a weak dopamine reuptake inhibitor and modafinil metabolite. There is no primary peer-reviewed literature on fluorene myristate itself, and even its exact structure and CAS identity are inconsistently reported by suppliers. This entry is therefore deliberately cautious and does not assert mechanisms or effects that have not been demonstrated for this specific molecule.
Foliglurax (developmental code PXT002331) is an orally active, brain-penetrant positive allosteric modulator of the mGlu4 receptor, a group III metabotropic glutamate receptor enriched at inhibitory synapses of the basal ganglia. It was developed by Prexton Therapeutics, later acquired by Lundbeck, as a non-dopaminergic treatment for Parkinson's disease, aiming to restore basal-ganglia balance and reduce both off time and levodopa-induced dyskinesia. In a phase 2 trial it produced dose-dependent reductions in daily off time that did not reach statistical significance on the primary endpoint. Foliglurax is a notable clinical test of the mGlu4 positive allosteric modulator concept for movement disorders.
Fosgonimeton is an injectable prodrug of dihexa, developed for Alzheimer's disease and taken through a 549-patient phase 2/3 trial that missed every endpoint. It is the most thoroughly tested member of a family whose founding mechanism papers were retracted for fabricated data. The chemistry is worth stating plainly because it is rarely stated at all: fosgonimeton is dihexa carrying a phosphate group on one hydroxyl and nothing else. The phosphate makes it soluble enough to inject; the body removes it, and what circulates and enters the brain is dihexa. Anyone reading about dihexa is therefore reading about a molecule whose active form has already been given to hundreds of patients.
Galanin(1-15) is an active N-terminal fragment of galanin that behaves as a distinct signaling entity through galanin receptor 1 and receptor 2 heteroreceptor complexes. On its own it produces strong anxiogenic and depression-like effects in rodents, often exceeding those of full-length galanin, yet paradoxically it enhances the antidepressant action of fluoxetine and can reverse fluoxetine-induced memory impairment. These effects depend on GalR1-GalR2 complexes interacting with serotonin 5-HT1A receptors in the raphe, hippocampus, and prefrontal cortex. It is a preclinical fragment of interest as both a mood modulator and an adjunct concept for antidepressant therapy.
Galanin(2-11), also known as AR-M1896, is a short galanin fragment corresponding to residues two through eleven of the peptide and is widely used as a galanin receptor 2 preferring agonist. As one of the few subtype-biased galanin tools, it has been central to dissecting which effects of galanin are mediated by GalR2 rather than GalR1, particularly in pain, mood, and neuroprotection. In the spinal cord and periphery it can be pronociceptive through GalR2, while GalR2 activation at the dorsal raphe is linked to increased serotonin and potential antidepressant effects. It is a preclinical research peptide.
Galmic is a macrocyclic nonpeptide galanin receptor agonist built on a rigid protein-surface-mimicking scaffold that displays galnon's pharmacophores in a fixed spatial arrangement. It has micromolar affinity for GalR1 and essentially no affinity for GalR2, and after systemic administration it blocks seizures, produces antidepressant-like effects, and reduces inflammatory pain behavior in rodents. Galmic is a preclinical chemical tool that helped establish that galanin receptors can be engaged by drug-like macrocycles. It has not advanced to human studies.
Galnon is a low-molecular-weight, systemically active nonpeptide galanin receptor agonist and one of the first small molecules shown to activate galanin receptors in vivo. It was designed from the known pharmacophores of galanin and displaces radiolabeled galanin from brain membranes with micromolar affinity while inhibiting adenylate cyclase, consistent with agonist action. In rodents it is anticonvulsant, anxiolytic, and modulates reward circuitry, making it a foundational pharmacological tool for probing the galaninergic system. Galnon remains a preclinical research compound with no human development.
Ginkgolide B is a diterpene lactone, one of the terpene trilactones found in the leaves and roots of the ginkgo tree (Ginkgo biloba). It has a complex cage-like structure built from six five-membered rings and a distinctive tert-butyl group, and it occurs in only small amounts within ginkgo extracts. In pharmacology it is best known as a potent and selective antagonist of platelet-activating factor, a property that has made it a valuable research tool and a candidate in studies of inflammation and neurological conditions.
Ginseng is the fleshy root of several slow-growing perennial plants in the genus Panax, part of the ivy family Araliaceae, and it is among the most widely used herbs in traditional East Asian medicine. The best known species are Asian ginseng (Panax ginseng) and American ginseng (Panax quinquefolius), both valued for a group of active saponins called ginsenosides. Ginseng is taken as a general tonic and is marketed to support energy, cognition, and resilience to stress, although clinical evidence for these uses is mixed.
Ginsenoside Rg1 is one of the most abundant and extensively studied saponins found in ginseng, particularly Panax ginseng and Panax notoginseng. It belongs to the protopanaxatriol group of dammarane-type triterpene glycosides and is a major contributor to the pharmacological profile attributed to ginseng. In laboratory and animal research, Rg1 has drawn attention chiefly for antioxidant, anti-inflammatory, and neuroprotective effects, and it is investigated as a candidate agent in models of neurodegenerative and cognitive disorders.
Ginsenosides are a class of natural steroid glycosides and triterpene saponins found almost exclusively in plants of the genus Panax, the source of ginseng. They are regarded as the principal active constituents behind ginseng's biological effects, and more than a hundred distinct ginsenosides have been characterized. Structurally most belong to the dammarane family and are divided into protopanaxadiol and protopanaxatriol types, with individual members such as Rb1, Rg1, and Re studied for antioxidant, anti-inflammatory, and neuroprotective activities.
GSK1034702 is a GlaxoSmithKline benzimidazolone marketed in the literature as an M1 allosteric agonist; it improved immediate recall in nicotine-abstinent smokers and was later shown to bind M1 bitopically and to lack muscarinic subtype selectivity.
GlaxoSmithKline built GSK189254 out of a benzazepine chemical series distinct from the imidazole-based H3 antagonists that came before it, and it turned into one of the field's most cited cognition tool compounds. It binds human H3 receptors with subnanomolar affinity and more than 10,000-fold selectivity over other targets tested, and PET-style binding studies confirmed it engages H3 receptors directly in postmortem Alzheimer's disease brain tissue. In rodents it raised acetylcholine, noradrenaline, and dopamine release in the cortex and hippocampus and improved performance across passive avoidance, water maze, object recognition, and attentional set-shifting tasks, a strong enough preclinical package that GSK explored it for Alzheimer's-related cognitive symptoms; it never emerged as a named clinical program, and the compound is now used mainly as a research standard rather than a drug candidate.
GTS-21, also known as DMXB-A, is an investigational drug that acts as a selective partial agonist at the alpha-7 subtype of nicotinic acetylcholine receptors. It is a synthetic derivative of anabaseine, a natural compound found in certain marine worms, and was developed as a candidate treatment for the cognitive problems of conditions such as schizophrenia and Alzheimer's disease [1][2]. Despite encouraging early laboratory results, it has not shown clear clinical benefit and has not advanced beyond mid-stage trials [2].
HA-966 is a small research-tool molecule, (±)-3-amino-1-hydroxypyrrolidin-2-one, that acts at the glycine co-agonist site of the NMDA glutamate receptor. It behaves as a partial agonist there, which in practice means it can dampen NMDA receptor activity (a functional antagonist) when the site is otherwise driven by glycine. It is used in labs to probe NMDA signaling rather than as a supplement.
Hemantane is a Russian aminoadamantane (a cage-shaped adamantane molecule carrying an amine group, the same chemical family as amantadine) developed at the Zakusov Institute of Pharmacology as an experimental antiparkinsonian and analgesic (pain-relieving) drug. It works through several linked actions at once: it is a low-affinity blocker of the NMDA glutamate receptor, it raises dopamine in the striatum, and it weakly and reversibly inhibits the enzyme MAO-B. It is essentially unknown outside Russian-language research and has no established use in Western medicine.
HER-096 is a brain-penetrating peptidomimetic derived from human CDNF (cerebral dopamine neurotrophic factor), developed by Herantis Pharma as a candidate disease-modifying therapy for Parkinson's. It mimics CDNF's cytoprotective biology in a small, stable molecule; it eases endoplasmic-reticulum stress by modulating the unfolded protein response, protects dopaminergic neurons, reduces alpha-synuclein aggregation, and calms neuroinflammation. Unlike the full CDNF protein, which had to be infused directly into the brain, HER-096 reaches the brain after a simple subcutaneous injection.
Hericene A is a hydrophobic hericerin-derived isoindoline compound from Hericium erinaceus that activates a pan-neurotrophic signaling pathway distinct from the classic NGF mechanism. In cultured hippocampal neurons it and its precursor N-de-phenylethyl isohericerin promoted extensive axon outgrowth and neurite branching even without serum, acting partly through a TrkB-independent route that converges on ERK1/2. Mice fed Hericium extract and hericene A showed increased neurotrophin signaling and significantly enhanced hippocampal memory, making hericene A a standout modern discovery in Lion's Mane neurobiology.
Hericenone C is an aromatic fatty-acid ester isolated from the fruiting body of Hericium erinaceus and one of the classic small-molecule inducers of nerve growth factor synthesis identified from Lion's Mane. Together with hericenones D and E it helped establish the scientific basis for the mushroom's traditional reputation as a nerve tonic. Unlike the mycelial erinacines, hericenones are relatively large and lipophilic and are thought to act largely peripherally rather than crossing the blood brain barrier efficiently.
Hericenone D is an aromatic fatty-acid ester from the fruiting body of Hericium erinaceus, one of the original nerve growth factor-inducing hericenones described from Lion's Mane. It is closely related to hericenones C and E and contributes to the neurotrophic activity attributed to fruiting-body extracts. Like its congeners it is considered to act predominantly in the peripheral nervous system rather than crossing the blood brain barrier.
Homotaurine, chemically 3-amino-1-propanesulfonic acid (3APS), is a small aminosulfonic acid that occurs naturally in certain marine red algae; it is a homolog of the amino acid taurine and a structural analog of the inhibitory neurotransmitter GABA, and it behaves as a GABA-A receptor modulator. Its pharmaceutical interest, however, comes from a different property: it is an anti-amyloid agent that binds soluble amyloid-beta and inhibits its aggregation into neurotoxic oligomers. Under the drug name tramiprosate it was carried into large phase 3 Alzheimer's disease trials that were negative overall, yet a subgroup signal tied to the APOE4 genotype survived the failure and drove a second act. That signal spawned a valine-conjugated prodrug, ALZ-801 (valiltramiprosate), now studied specifically in APOE4/4 homozygotes with early Alzheimer's disease. Homotaurine is also sold as a nutraceutical for memory, where its efficacy remains unproven.
HT-0712 (betamilast) is a PDE4 inhibitor purpose-engineered to be a memory drug. Designed across Inflazyme, Helicon and Dart NeuroScience, it targets the CREB memory pathway with a wider therapeutic window than the notoriously emetic rolipram. In animals it selectively boosts long-term (not short-term) memory in normal and aged mice, and it reached Phase 2 testing in age-associated memory impairment, making it the most deliberately memory-focused candidate in the PDE4 class.
A selective M1 partial agonist from Heptares that improved memory and attention in healthy volunteers and Alzheimer's patients, and was halted in 2018 over a tumour finding in monkeys rather than anything seen in people.
Hydergine is the trade name for ergoloid mesylates, a mixture of methanesulfonate salts of several hydrogenated ergot alkaloids derived from the ergot fungus. Developed by Albert Hofmann at Sandoz, it was long prescribed for age-related cognitive decline and cerebral insufficiency and is often cited as one of the earliest nootropics. Reviews of its use in dementia have found modest overall effects and good tolerability, though its efficacy remains uncertain.
Idalopirdine is a potent, selective serotonin 5-HT6 receptor antagonist developed by H. Lundbeck (as Lu AE58054) as an adjunctive symptomatic treatment for Alzheimer's disease. By blocking 5-HT6 receptors, which are expressed almost exclusively in the central nervous system and concentrated in the hippocampus and cortex, it disinhibits cholinergic, glutamatergic and monoaminergic transmission relevant to memory. A phase 2 trial (LADDER) in donepezil-treated moderate Alzheimer's disease showed a significant cognitive benefit, but the larger phase 3 STARSHINE, STARBEAM and STARBRIGHT programme failed to replicate it. Idalopirdine is discontinued for cognition and is now referenced primarily as a pharmacological tool and cautionary case study.
IFB-088 (also called icergustat, related to the tool compound Sephin1) is an experimental small molecule that inhibits the regulatory subunit of protein phosphatase 1 known as PPP1R15A (GADD34). By blocking this subunit it prolongs the cell's integrated stress response, and it has been studied for neurodegenerative and demyelinating conditions such as certain peripheral neuropathies. It is an investigational compound, not an approved drug.
Indeloxazine was developed and marketed in Japan from the late 1980s, under brand names including Elen and Noin, as a dual serotonin/norepinephrine reuptake inhibitor aimed at a use case Western antidepressants of the era largely ignored: the depression, apathy and cognitive slowing that follow a stroke. It stayed almost entirely confined to the Japanese market and pharmacology literature, mechanistically an early dual-reuptake antidepressant that never secured a Western indication despite predating some Western SNRIs. More recently its resolved (+)-isomer, given the separate code AS1069562, has been revisited in Japanese pain research as a serotonin-transporter-mediated analgesic for neuropathic and myalgic pain, giving this obscure Japanese post-stroke drug an unexpected second research life decades later.
Intepirdine is a selective serotonin 5-HT6 receptor antagonist originally discovered at GlaxoSmithKline as SB-742457 and later licensed to Axovant Sciences as RVT-101 for Alzheimer's disease and dementia with Lewy bodies. Like other compounds in its class it was intended to enhance cognition by disinhibiting cholinergic and glutamatergic signaling in cortex and hippocampus. A phase 2 study suggested a modest global and cognitive benefit, but the pivotal phase 3 MINDSET trial in mild-to-moderate Alzheimer's disease was clearly negative. Its high-profile failure in 2017 effectively ended enthusiasm for 5-HT6 antagonism as a standalone dementia strategy.
IPAP is a little-studied member of the PPAP/BPAP family of synthetic 'enhancer' compounds that grew out of Jozsef Knoll's work on selegiline (the pharmacologist who first described this drug class). Where PPAP carries a plain phenyl ring and BPAP a benzofuran, IPAP carries an indole ring, making it the tryptamine-flavored cousin of the series. Enhancers do not force neurotransmitter out of neurons the way stimulants do; they nudge catecholaminergic and serotoninergic neurons to release a little more dopamine, norepinephrine, and serotonin only when those neurons naturally fire. IPAP itself is barely characterized, so almost everything that can be said about it is inferred from its better-studied relatives.
Irdabisant (CEP-26401) is a potent, highly selective histamine H3 receptor antagonist and inverse agonist developed by Cephalon. Because the H3 receptor is largely an inhibitory autoreceptor and heteroreceptor that restrains release of histamine and other arousal-related neurotransmitters, blocking it disinhibits wake-promoting signaling; in preclinical models irdabisant showed robust wake-promoting activity and improved short-term memory at low doses, alongside favorable central nervous system drug-like properties and high selectivity over other histamine receptor subtypes. It was studied as a candidate cognition-enhancing and wakefulness-promoting agent for conditions such as cognitive impairment and schizophrenia. Early human studies characterized its pharmacokinetics and pharmacodynamics, including dose-dependent effects on sleep, but the compound advanced only into early clinical trials and was never brought to market.
Ispronicline traces its chemistry back to nicotine research originally funded by tobacco company R.J. Reynolds, which spun off its pharmaceutical research arm into Targacept in the late 1990s. The resulting compound was a partial agonist at alpha4beta2 neuronal nicotinic receptors, designed to capture nicotine's attention- and memory-enhancing effects without its addictive and cardiovascular baggage. AstraZeneca partnered with Targacept and pushed ispronicline (as AZD3480) into a Phase IIb dose-finding trial for mild-to-moderate Alzheimer's disease as well as separate studies for adult ADHD. The Alzheimer's trial, published in 2011, failed to show a robust cognitive benefit, and AstraZeneca discontinued the partnership around 2010-2011, part of a broader collapse of the nicotinic-receptor cognition-enhancement field that also claimed several competing programs.
Istradefylline is a selective adenosine A2A receptor antagonist used as an add-on to levodopa-based therapy in adults with Parkinson's disease. It is taken to reduce daily off episodes, the stretches of the day when dopaminergic medication wears off and motor symptoms return [1][2]. Structurally a xanthine derivative, it was the first drug of its class to reach the market and acts through a non-dopaminergic pathway distinct from conventional Parkinson's treatments [1].
JJC8-088 is a modafinil-derived dopamine transporter blocker synthesised at NIDA that was first published as an atypical, low abuse liability lead for cocaine use disorder and was then reclassified by its own lab as the cocaine-like one [2]; rats and monkeys self-administer it, no human has ever taken it, and its role in the literature today is mostly as the typical comparator against its atypical sibling JJC8-091 [4].
JNJ-40411813 (also known as ADX71149) is an orally active positive allosteric modulator of the mGlu2 receptor, developed jointly by Janssen and Addex Therapeutics as a potential treatment for schizophrenia and mood disorders. Unlike full agonists such as pomaglumetad, it enhances the receptor's response to endogenous glutamate only where and when glutamate is released, an approach intended to preserve physiological signalling patterns. It reached phase 2 testing for schizophrenia and for anxious depression, showing an acceptable safety profile and secondary-endpoint signals despite missing primary endpoints. The compound is a leading example of the shift from mGlu2/3 agonism to subtype-selective allosteric modulation.
Ketamine is a dissociative anesthetic that turned into the most important antidepressant discovery in fifty years. It blocks the NMDA glutamate receptor, which is what produces anesthesia without suppressing breathing and made it a battlefield and emergency drug from 1970 onward [1]. The finding that matters now came around the turn of the century: a single sub-anesthetic dose can lift severe, treatment-resistant depression within hours rather than weeks, an effect no monoamine antidepressant produces [3][4]. Its S-enantiomer, esketamine, is approved for that use as a nasal spray. Cognition is the more nuanced half of the story; repeated supervised infusions have not been shown to impair it and several measures improve as depression lifts, while heavy unsupervised use is reliably associated with memory problems [28][30]. It remains a controlled substance with real dependence and bladder toxicity risk outside clinical use.
A ketone ester is an ingestible compound, most commonly (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, that rapidly and transiently raises blood D-beta-hydroxybutyrate (BHB) without requiring fasting or a ketogenic diet [1][2]. By delivering ketone bodies directly, it induces 'acute nutritional ketosis' and provides an alternative oxidative fuel to glucose, with studied applications in endurance performance, metabolic health and cognition [1][3].
L-Clausenamide, or (-)-clausenamide, is a pyrrolidinone alkaloid isolated from the leaves of Clausena lansium (wampee) and studied in China as a nootropic and neuroprotective anti-dementia drug candidate [1]. It is the eutomer of the clausenamide enantiomers, improving learning and memory through multi-target actions including modulation of intracellular calcium, cholinergic support, enhancement of synaptic plasticity and long-term potentiation, and antioxidant protection [1]. In cellular and animal models it protects neurons against beta-amyloid, okadaic-acid and ischemic injury and inhibits ferroptosis in dopaminergic neurons [2][3][4].
L-DOPA, also called levodopa, is a naturally occurring amino acid that serves as the immediate precursor to the catecholamine neurotransmitters dopamine, norepinephrine, and epinephrine. Unlike dopamine itself, it can cross the blood-brain barrier, where enzymes convert it into dopamine, which is why it became the cornerstone drug for treating Parkinson's disease. It occurs in nature in certain legumes, most notably the velvet bean Mucuna pruriens, and is usually given together with an enzyme inhibitor such as carbidopa to improve its delivery to the brain.
L-Threonic acid is a four-carbon sugar acid and a natural metabolite of ascorbic acid, better known as vitamin C. On its own it has drawn little study, but its magnesium salt, magnesium L-threonate, has become a focus of research because it can raise magnesium levels in the brain. Sold as the branded ingredient Magtein, magnesium L-threonate is marketed as a supplement aimed at memory and cognition, and threonate has separately been examined in laboratory work on hair biology.
Latrepirdine, better known by its Soviet-era trade name Dimebon, is a multi-target small molecule originally marketed in Russia as a non-selective antihistamine and later repurposed as a candidate cognition enhancer. Among its many actions it is a moderate-affinity 5-HT6 receptor antagonist, and this activity is thought to contribute to its acute pro-cognitive effects in animal models. After an early positive Russian trial in Alzheimer's disease generated intense interest, large international phase 3 studies in both Alzheimer's disease and Huntington's disease were negative. It is now studied mainly as a promiscuous pharmacological tool and a lesson in multi-target drug development.
Linopirdine took a completely different route to boosting acetylcholine than anything else in this collection; instead of blocking the enzyme that breaks ACh down, DuPont built it to block KCNQ2/KCNQ3 potassium channels, the so-called M-channel, which in turn triggers broad neurotransmitter release, acetylcholine included, across the brain. Preclinical work in the late 1980s looked strong enough that DuPont pushed it into Alzheimer's clinical trials, but the results in patients were equivocal; the drug needed high doses to meaningfully block the M-current, and those doses caused cholinergic overstimulation side effects like tremor. The program was ultimately discontinued, but linopirdine's real legacy is scientific rather than commercial, it became the founding tool compound for an entire generation of KCNQ channel research, directly enabling more selective descendants like XE-991 and eventually helping validate KCNQ as a target that led to the anticonvulsant retigabine.
Lisuride is an ergoline (ergot-derived) drug that acts as a dopamine D2-like receptor agonist while also blocking the 5-HT2B serotonin receptor. It is used medically for Parkinson's disease and for prolactin-related disorders, and unlike some related ergolines it is non-hallucinogenic at therapeutic use. Its character is that of a dopamine agonist with a favorable serotonin-receptor profile compared with older ergots.
LIT-001 is the first non-peptide oxytocin receptor agonist that reaches the brain and changes behaviour after an ordinary injection into the body, rather than having to be delivered into the skull. Oxytocin itself is a therapeutic dead end for brain use for three separate reasons, and this molecule was built to defeat all three at once. It has never been given to a human being.
Luteolin is a naturally occurring flavone, a subclass of flavonoid, that carries a yellow color and is present in many plants used as foods and herbs, including celery, parsley, thyme, chamomile, and oregano. It has been studied in the laboratory for antioxidant, anti-inflammatory, and anticancer activity, although solid human clinical evidence is limited. It was first isolated in 1829 from the dye plant Reseda luteola.
LY2033298 is a preclinical positive allosteric modulator of the M4 muscarinic acetylcholine receptor; it was the first small molecule selective enough to test whether activating M4 on its own could produce an antipsychotic effect.
LY341495 is a potent and selective orthosteric antagonist of group II metabotropic glutamate receptors (mGlu2 and mGlu3) developed by Eli Lilly, widely used as the standard pharmacological tool for blocking these receptors. By preventing autoreceptor-mediated suppression of glutamate release, it enhances excitatory transmission and produces rapid antidepressant-like effects in animal models, mechanistically overlapping with ketamine. It has become a key probe for research into fast-acting antidepressants and stress resilience. LY341495 is significant as the reference mGlu2/3 antagonist against which newer compounds are compared.
LY379268 is a highly potent and selective orthosteric agonist of group II metabotropic glutamate receptors (mGlu2 and mGlu3) developed by Eli Lilly as a research tool and neurotherapeutic candidate. It became one of the most influential probes for studying how presynaptic glutamate autoreceptors regulate addiction, neuroprotection and excitatory signalling. In animal models it robustly suppresses drug-seeking and cue-induced relapse for cocaine, nicotine and other substances, and it protects neurons against excitotoxic and demyelinating insults. Although never developed as a marketed drug, LY379268 remains a cornerstone compound in metabotropic glutamate neuroscience.
LY392098 was an early entry in Eli Lilly's biarylpropylsulfonamide AMPA potentiator series, and it did double duty in the company's research: as a tool for studying prefrontal cortical electrophysiology, and as one of the first pieces of evidence that boosting AMPA signaling could act like an antidepressant. In 2001 Lilly researchers published a trio of papers showing it potentiated AMPA currents selectively, without touching NMDA or kainate receptors, and reduced immobility in the forced swim test at a minimum effective dose of 0.5 mg/kg without moving serotonin or norepinephrine levels; a genuinely different antidepressant mechanism years before ketamine made glutamate a household word in psychiatry. Less potent than its stablemate LY404187, LY392098 stayed a research compound and was never taken into human trials as far as the public record shows.
LY404187 was one of the most potent compounds to come out of Eli Lilly's early-2000s AMPA receptor potentiator program, a biarylpropylsulfonamide engineered to suppress receptor desensitization with a distinctive, slowly-growing time course unlike anything seen with older potentiators like cyclothiazide or aniracetam. Researchers used it to prove, in a fairly dramatic way, that AMPA potentiation alone could switch on broad swaths of brain metabolic activity; a 2004 study showed it drove cerebral glucose utilization and c-fos expression widely across the rat brain. It was also tested alongside LY503430 for neurotrophic rescue in Parkinson's disease models. Despite the strong pharmacology, LY404187 stayed a Lilly screening and mechanism-validation tool rather than a clinical candidate, and there's no record of it ever reaching human testing.
LY451646 was one of Eli Lilly's AMPA receptor potentiators explored as a fundamentally different kind of antidepressant, one that worked through fast glutamatergic signaling rather than the serotonin/norepinephrine route every SSRI and SNRI takes. It behaved like an antidepressant in classic rodent despair tests, and chronic dosing drove roughly a 45 percent jump in hippocampal progenitor cell proliferation along with increased BDNF and TrkB expression, the same neuroplasticity signature later associated with ketamine. Development stalled in the mid-2000s; LY451646 and its close relative LY451395 both showed intrinsic partial-agonist activity at high concentrations that raised seizure risk, a liability that appears to have kept it (and much of Lilly's ampakine series) out of the clinic. In hindsight it was chasing the same glutamate-antidepressant idea that ketamine would validate roughly a decade later, just through a different receptor.
LY503430 was Eli Lilly's early-2000s AMPA receptor potentiator, built to test whether boosting glutamatergic signaling could protect and even rescue dopamine neurons in Parkinson's disease. In rodent models it reduced neurotoxicity from both 6-hydroxydopamine and MPTP lesions, and remarkably still helped when dosing started days after the lesion was already established; a neurotrophic effect, not just a protective one. Lilly developed a cGMP synthesis route specifically to fund first-human-dose trials, but no published clinical data ever surfaced, and the compound appears to have been quietly dropped, likely a casualty of the same epileptogenic and safety concerns that stalled Lilly's whole AMPA potentiator program. It survives today only as a pharmacology reference compound.
M617 is a synthetic chimeric galanin analog that acts as a galanin receptor 1 preferring agonist and is used as a subtype-selective research tool. Built from the galanin N-terminus fused to a bradykinin-derived segment, it engages GalR1 to produce antinociception in central pain circuits and to improve glucose handling in diabetic rodents by enhancing insulin signaling and glucose-transporter activity in muscle. As one of the more GalR1-selective agonists available, M617 has been valuable for isolating GalR1-specific functions in pain and metabolism. It is a preclinical peptide with no clinical use.
Magnesium is an essential dietary mineral and the second most abundant positively charged ion inside human cells. It serves as a cofactor for hundreds of enzymes, is required for every reaction that uses ATP, and is central to nerve conduction, muscle contraction, and heart rhythm. Low magnesium status has been linked to several chronic diseases, and magnesium is widely used both as a nutritional supplement and as a medicine.
MAP4343 (3β-methoxypregnenolone) is a synthetic derivative of the endogenous neurosteroid pregnenolone in which the 3β-hydroxyl group is replaced by a methyl ether, developed by the French steroid pharmacologist Étienne-Émile Baulieu and the biotechnology company Mapreg. Unlike classical neurosteroids that modulate ligand-gated ion channels, MAP4343 acts on microtubule-associated protein 2 (MAP2; a structural protein that governs the assembly and stability of neuronal microtubules), where it promotes tubulin polymerization and restores microtubule dynamics. It has been investigated as a novel, mechanistically distinct antidepressant and anti-addiction candidate, showing rapid and durable antidepressant-like effects in rodent and tree shrew stress models and having advanced into early clinical development. As of the mid-2020s it remains an investigational agent without regulatory approval.
Masupirdine is a potent, selective serotonin 5-HT6 receptor antagonist developed by Suven Life Sciences as SUVN-502 for cognitive deficits in Alzheimer's disease. It was distinctive as the first compound in its class tested on a background of both donepezil and memantine, reflecting real-world moderate Alzheimer's disease management. The pivotal phase 2 proof-of-concept study did not meet its prespecified cognitive endpoint, although exploratory post hoc analyses suggested that concurrent memantine may have masked a benefit. Suven has since pivoted masupirdine toward agitation in dementia rather than core cognition.
Mavoglurant (developmental code AFQ056) is an orally active, selective negative allosteric modulator of the metabotropic glutamate receptor subtype 5 (mGlu5). It was advanced by Novartis primarily for levodopa-induced dyskinesia in Parkinson's disease and for fragile X syndrome, where excess mGlu5 signalling is implicated in synaptic pathology. Randomized trials demonstrated a measurable anti-dyskinetic signal in Parkinson's disease without worsening motor control, but pivotal fragile X and language-learning studies failed to separate from placebo. It remains an important pharmacological probe of group I metabotropic glutamate signalling and a case study in the difficulty of translating mGlu5 blockade into clinical benefit.
McN-A-343 is a quaternary muscarinic agonist that served for decades as the standard tool for identifying M1-mediated responses, and which is now understood to owe that apparent selectivity to uneven efficacy and to a second, allosteric binding site rather than to selective binding.
Meclofenoxate, also known as centrophenoxine, is a nootropic compound classified as a cholinergic agent, made by combining dimethylethanolamine (DMAE) with para-chlorophenoxyacetic acid. Developed in the late 1950s, it has been used, mainly in Europe and Asia, as a prescription drug for age-related cognitive decline and dementia, and it is sold elsewhere as an unapproved dietary supplement marketed for memory and mental alertness [1][4]. Research, much of it older or preclinical, has examined its effects on memory, brain aging, and the accumulation of the cellular waste pigment lipofuscin [2].
Mesocarb, marketed in the Soviet Union as Sydnocarb, was synthesized in the early 1970s as a stimulant with a smoother pharmacological profile than amphetamine. Where classic amphetamines flood synapses by forcing dopamine release, sydnocarb works mainly by blocking the dopamine transporter directly, and it turned out to be an unusually selective one; by some later measurements it is among the most DAT-selective reuptake inhibitors ever characterized. Soviet and later Russian medicine used it for over 30 years to treat narcolepsy, asthenia, apathy and attention problems in children, effectively occupying the clinical niche that methylphenidate and amphetamine fill in the West, but it was withdrawn as a licensed Russian pharmaceutical in 2008 as stimulant controls tightened, and it is now better known internationally as a doping-control flag than as a treatment.
Metergoline is an ergoline (an ergot-derived compound) that works mainly as a potent antagonist at serotonin receptors, blocking both 5-HT1 and 5-HT2 subtypes, while also carrying some dopamine-agonist activity. Because it blocks serotonin so broadly, it is used as a research tool to probe serotonergic function and as a prolactin-lowering agent. It is not a stimulant or a mood booster; its character is that of a serotonin blocker.
A short-acting inhaled muscarinic agonist used for exactly one job, the bronchial challenge test, which measures whether a person's airways narrow more readily than they should.
Methylphenylpiracetam (MPP) is a methylated analogue of phenylpiracetam developed at the Latvian Institute of Organic Synthesis, and its most studied stereoisomer, E1R, is a positive allosteric modulator of the sigma-1 receptor [1]. In mice, E1R enhances memory retention and reverses scopolamine-induced cognitive impairment without altering locomotor activity, effects abolished by the selective sigma-1 antagonist NE-100 [1]. Unlike its parent phenylpiracetam, which is primarily a dopaminergic psychostimulant, MPP is characterized as a non-stimulant cognition enhancer acting through sigma-1 chaperone signaling [1].
Metrifonate has one of the stranger backstories in Alzheimer's drug history; it started life decades earlier as an antischistosomal insecticide-derived organophosphate sold as Bilarcil, and only later did researchers realize its slow, pseudo-irreversible acetylcholinesterase inhibition made it a candidate for boosting acetylcholine in Alzheimer's disease. Bayer ran it through large placebo-controlled Phase III trials where it produced genuine, statistically significant cognitive improvement over placebo, real efficacy that few of its competitors in this archive ever achieved. Then, deep into trials, roughly twenty patients developed neuromuscular dysfunction and life-threatening respiratory paralysis, apparently related to how chronic organophosphate exposure sensitizes patients to subsequent anesthetic or neuromuscular-blocking agents; Bayer halted the program and withdrew its FDA application in 1997, turning a drug with real cognitive benefit into a cautionary tale about repurposing organophosphates for chronic dosing.
Mibampator (LY451395) is a biarylpropylsulfonamide positive allosteric modulator of AMPA receptors developed by Eli Lilly as a cognition- and behavior-focused clinical candidate. It slows AMPA-receptor deactivation, with an efficacy strongly shaped by the auxiliary TARP proteins associated with the receptor. It reached a randomized controlled trial for agitation and aggression in Alzheimer's disease, where it did not separate from placebo on the primary outcome but showed a signal on a secondary frontal-behavior measure. It is an instructive example of a clinically tested AMPA potentiator.
MIF-1 (Pro-Leu-Gly-NH2), also called melanostatin, is a small endogenous tripeptide made in the body. It was first recognized as the hypothalamic factor that inhibits release of melanocyte-stimulating hormone from the pituitary, and it was later found to act in the brain as a positive allosteric modulator of dopamine D2 receptors. Because of that dopamine-enhancing action it has been studied as a potential treatment for depression and Parkinson's disease.
Milameline was Parke-Davis and Roussel-Uclaf's shot at treating Alzheimer's disease by stimulating muscarinic receptors directly instead of propping up acetylcholine with a cholinesterase inhibitor. It is a partial agonist with roughly equal affinity at all five muscarinic subtypes, which was the deliberate choice: no subtype selectivity, just enough intrinsic activity to signal without saturating the system. The preclinical package was strong for its era. It reversed spatial memory deficits in rats with lesioned forebrain cholinergic neurons, raised cortical blood flow, desynchronised the EEG in both rats and rhesus monkeys in the pattern that reads as increased arousal, and rescued scopolamine-impaired attention in monkeys. Then the dose window closed. In Alzheimer's patients, 1 mg every six hours was fine, 2 mg was tolerated by most people, and 2.5 to 3 mg brought sweating, hypersalivation, nausea, diarrhoea, hypotension and, notably, parkinsonian signs including cogwheeling, tremor and a shuffling gait; that study was stopped after the fourth 3 mg dose. The pivotal 52-week trial across 38 centres was then terminated early when an interim analysis projected it would not work. It never worked, and it was never approved.
MK-0777 was a Merck compound built to be a benzodiazepine-like drug without the sedation; it selectively potentiated GABA-A receptors carrying the alpha2 or alpha3 subunit instead of hitting alpha1 (the subunit responsible for benzodiazepine sedation and abuse liability). The idea came out of University of Pittsburgh postmortem work showing that GABA neurotransmission onto pyramidal cells in the schizophrenic prefrontal cortex is weakened, which was proposed as a root cause of the working-memory deficits in the disease. A small 2008 open-label-adjacent proof-of-concept trial in chronic schizophrenia patients found real improvements on working-memory tasks and increased frontal gamma power, which made a fair bit of noise in the field. A larger, properly randomized follow-up then failed to replicate the benefit, and Merck quietly let the program lapse; it never advanced past early Phase II.
MK-7622 is a Merck M1-selective muscarinic positive allosteric modulator that reached a phase 2 Alzheimer's trial as an add-on to acetylcholinesterase inhibitors and was stopped at a futility interim analysis.
Morphodrol is a vendor name for morpholin-3-yl(diphenyl)methanol, also written 3-(diphenylhydroxymethyl)morpholine, CAS 26581-79-3. Structurally it is pipradrol with one ring carbon swapped for an oxygen, which places it in the same family as the research chemicals desoxypipradrol (2-DPMP) and diphenylprolinol (D2PM) [3]. That family resemblance is the entire basis of everything claimed for it. Searches under the vendor name, the systematic names, the older nomenclature and the CAS number return nothing on PubMed, and PubChem holds no literature cross reference for the compound; there is no binding assay, no animal study, no case report and no human data. It is sold as a laboratory research chemical and is accurately described as an untested one.
MRZ-9547 is the R-enantiomer of phenylpiracetam (R-fonturacetam), developed by Merz Pharmaceuticals as a selective dopamine transporter (DAT) inhibitor for the fatigue and reduced motivation of Parkinson's disease [1][2]. In rats it dose-dependently increases effort-related responding and reverses motor deficits in Parkinson models, moderately raising striatal dopamine release, while its L-enantiomer MRZ-9546 is far less active [1][2]. It should not be conflated with racemic phenylpiracetam: MRZ-9547 is a single, defined enantiomer studied specifically as a DAT-based anti-fatigue agent [2].
The fungal alkaloid that muscarinic receptors are named after; it has no therapeutic use and matters today as the toxin behind Inocybe and Clitocybe mushroom poisoning.
One of the two original green mamba muscarinic toxins; it binds M1 and M4 near-irreversibly and acts as a slow muscarinic agonist, but it is markedly less selective than its early reputation suggested.
A 65 residue green mamba toxin used as the standard M4-preferring muscarinic antagonist, with the significant caveat that it binds several alpha adrenoceptors just as tightly.
N-Acetyl Selank is an acetylated analog of Selank, a synthetic heptapeptide with the sequence Thr-Lys-Pro-Arg-Pro-Gly-Pro that is derived from the immune-modulating peptide tuftsin. Selank was developed at the Institute of Molecular Genetics of the Russian Academy of Sciences and is used in Russia as an anxiolytic and nootropic, typically delivered as a nasal spray. The N-acetyl modification is intended to increase resistance to enzymatic breakdown; it has been studied far less than the parent peptide, and neither form is approved outside a small number of countries.
N-Acetyl Semax is an acetylated analog of Semax, a synthetic heptapeptide with the sequence Met-Glu-His-Phe-Pro-Gly-Pro that is based on the ACTH(4-10) fragment of adrenocorticotropic hormone. Developed and studied extensively in Russia, Semax is used there as a nootropic and neuroprotective agent, including in stroke and cognitive disorders, and appears on the Russian list of essential medicines. The N-acetyl modification is meant to improve stability; it is far less studied than the parent peptide, and neither form is approved in most countries.
N-Methyl-Cyclazodone is the N-methylated analog of cyclazodone, a stimulant research chemical from the pemoline-related oxazolidinone family. Adding a methyl group to the ring nitrogen is a small structural tweak that is presumed to preserve the parent's dopaminergic, focus-oriented stimulant character. It is an obscure gray-market compound with essentially no dedicated human research.
N-Methyl-Cypenamine is the N-methyl analog of cypenamine (2-phenylcyclopentylamine), a catecholaminergic CNS stimulant research chemical. Like its parent it is presumed to act as a norepinephrine-dopamine releaser and reuptake inhibitor, giving energy and mild mood elevation. It is obscure, gray-market, and lightly studied in humans.
NADH is the reduced form of nicotinamide adenine dinucleotide (NAD+), a coenzyme found in all living cells that carries electrons in the reactions of energy metabolism. By shuttling reducing equivalents into the mitochondrial electron transport chain, it is central to the production of ATP, the cell's energy currency. NADH is also sold as a dietary supplement, most often promoted for energy and fatigue, although clinical evidence for oral supplementation is limited and mixed.
NAX 810-2 is a second-generation galanin analog engineered to prefer galanin receptor 2 over receptor 1, developed to preserve the anticonvulsant and analgesic benefits of galanin signaling while avoiding the hyperglycemia caused by GalR1-preferring predecessors. It has roughly fifteen-fold selectivity for GalR2, blocks seizures in multiple rodent models after intravenous dosing, and is analgesic across inflammatory and neuropathic pain assays. Crucially, it does not impair insulin secretion or raise growth hormone, giving it a cleaner metabolic profile than NAX-5055. It was framed as a first-in-class analgesic and antiseizure candidate.
NAX-5055, also known as Gal-B2, is a systemically active, metabolically stable galanin analog engineered to cross the blood-brain barrier by combining cationization with position-specific lipidization. It is a GalR1-preferring agonist with low-nanomolar receptor affinity and potent anticonvulsant activity in multiple rodent seizure models, including models of pharmacoresistant epilepsy. It was positioned as a potential first-in-class antiepileptic neuropeptide therapeutic. NAX-5055 also engages peripheral GalR1 to raise blood glucose, which shaped subsequent development toward GalR2-preferring successors.
Neboglamine (also called nebostinel, development code CR-2249) is an investigational compound that acts as a positive modulator of the glycine site on the NMDA glutamate receptor. Developed by the Italian company Rottapharm, it was studied as a potential cognition enhancer and antipsychotic, and later as a treatment for cocaine dependence. It reached early-phase clinical testing but is not an approved medicine, and human evidence is limited.
Nebracetam (development code WEB 1881 FU) is an investigational nootropic of the racetam family that was studied mainly in Japan as a potential cognition enhancer. Chemically a pyrrolidinone related to piracetam, it is distinguished from most racetams by acting as a direct agonist at the M1 muscarinic acetylcholine receptor, alongside pronounced cholinergic and neuroprotective effects in preclinical models of memory impairment and cerebral ischemia. It was explored in such models but did not become an approved medicine.
Neurotrophin-3 (NT-3) is a naturally occurring protein belonging to the neurotrophin family, which also includes nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). It supports the survival, growth, and differentiation of developing neurons and helps maintain certain nerve cells in the mature nervous system. Because of these roles, recombinant NT-3 has been investigated as a therapy for nerve and gastrointestinal disorders, although it is not an approved or consumer product.
NGX267 started life at Neurogen Corporation and was carried forward by TorreyPines Therapeutics in the mid-to-late 2000s as a dual M1/M4 muscarinic agonist with two proposed uses: improving cognition in Alzheimer's disease and treating xerostomia (severe dry mouth), a side effect common in Sjogren's syndrome and antipsychotic treatment. Its first-in-human dose-escalation study, published in 2009, used an adaptive statistical design that ended up getting cited almost as often for its methodology as for the drug itself. TorreyPines' broader pipeline stalled soon after, the company dissolved and merged into Raptor Pharmaceutical around 2009-2010, and NGX267 was left without a sponsor to carry it into later-phase trials.
nicotine is a genuinely nootropic nicotinic agonist with a small, real, meta-analysis-backed edge on attention and psychomotor speed (bigger in cholinergic-deficit brains than in healthy young ones), delivered through α4β2, α6 and α7 receptors; the honest catch is that it's an addictive drug whose habit-forming power scales with how fast you take it, so the entire case for using it rests on non-combusted low-dose delivery and clear eyes about dependence.
Nle1-Angiotensin IV is a six-amino-acid peptide, angiotensin IV with its first residue swapped for norleucine. It is the research compound the whole dihexa and fosgonimeton family grew out of, and it improved memory in rats in several laboratories through the late 1990s and 2000s. ⚠️ It is almost always described as an AT4 receptor agonist, and both halves of that are wrong. The AT4 receptor turned out to be IRAP, an enzyme rather than a receptor, and this peptide blocks its active site. It is an enzyme inhibitor that has been called a receptor agonist for thirty years out of habit. Every rodent experiment injected it directly into the brain, because it does not survive the bloodstream or cross into the brain on its own.
NPAP is a little-studied member of the PPAP/BPAP family of synthetic 'enhancer' compounds that came out of Jozsef Knoll's work on selegiline (the pharmacologist who first described this drug class). The series shares a 2-propylaminopentane backbone and differs by the aromatic ring at one end: PPAP carries a plain phenyl, BPAP a benzofuran, IPAP an indole, and NPAP a naphthalene (a larger, two-ring aromatic). Enhancers do not force neurotransmitter out of neurons the way stimulants do; they coax catecholaminergic and serotoninergic neurons into releasing a little more dopamine, norepinephrine, and serotonin only when those neurons naturally fire. NPAP itself is barely characterized, so nearly everything that can be said about it is inferred from its better-studied relatives.
Otsuka Pharmaceutical in Japan built OPC-14523 to hit two antidepressant-relevant targets in one molecule, sigma receptors and the 5-HT1A receptor, without directly blocking the serotonin transporter the way an SSRI does. In rodent screens it cut immobility in the forced swim test, increased dorsal raphe serotonergic neuron firing with repeated dosing, and reversed both scopolamine-induced and age-associated memory impairment, a combination antidepressant and pro-cognitive profile that made it a heavily cited pharmacology tool through the early 2000s. There is no public record of it reaching a pivotal human depression trial; Otsuka's psychiatric pipeline moved in other directions, and OPC-14523 stayed a preclinical proof-of-concept rather than becoming a marketed drug.
Org 26576 is an investigational ampakine from the Organon (later Merck) program; a positive allosteric modulator of AMPA-type glutamate receptors that enhances hippocampal AMPA responses in an exposure-dependent way. Unusually for the class it reached multiple human trials in mood and attention disorders, where it produced signals of improved executive function and processing speed alongside a distinctive neuroendocrine profile of raised growth hormone and lowered cortisol.
Oxotremorine is a non-selective muscarinic agonist used in the laboratory to produce a reproducible cholinergic syndrome in rodents: tremor, hypothermia, salivation and analgesia.
p-Fluoro-Deprenyl is a para-fluoro analog of selegiline (deprenyl), a selective inhibitor of monoamine oxidase B (MAO-B, an enzyme that breaks down dopamine and related amines in the brain). It is largely a research compound of interest for the catecholaminergic and neuroprotective effects seen with the selegiline family. The fluorine substitution is mainly explored for tuning metabolism and, in labeled form, for brain imaging of MAO-B.
P7C3 is an investigational neuroprotective compound of the aminopropyl carbazole class, studied only in laboratory and animal research. It is proposed to work by boosting cellular NAD+ through activation of the enzyme NAMPT, which helps preserve the survival of newly formed and stressed neurons. In animal models it has shown protective effects in conditions such as stroke, traumatic brain injury, and neurodegeneration, but it is not an approved medicine.
P7C3-A20 is the most-used member of the P7C3 family of aminopropyl carbazoles, a series that protects neurons in a striking range of animal injury models: traumatic brain injury, stroke, Parkinson's models, nerve injury and more. ⚠️ Its mechanism is described everywhere as activation of NAMPT, the enzyme that limits NAD regeneration. No binding or potency constant at that enzyme has ever been published for it, and the originating laboratory now describes the series as NAD-stabilising rather than NAMPT-activating. ⚠️ The only fully independent laboratory test of it in culture was negative twice: it failed to protect neurons in three separate systems, and it was toxic at higher concentrations.
PACAP, short for pituitary adenylate cyclase-activating polypeptide, is a naturally occurring neuropeptide that acts as a hormone, neurotransmitter, and neuromodulator. Encoded by the ADCYAP1 gene and closely related to vasoactive intestinal peptide, it signals through G protein-coupled receptors to raise cellular cAMP and takes part in the stress response, circadian timing, and neuroprotection. It has become a prominent target in migraine research, since infusing PACAP can trigger migraine-like attacks in susceptible people.
PEPA came out of Japan's National Institute of Neuroscience in the mid-1990s as a sulfonamide-based AMPA receptor potentiator, and researchers there quickly realized it was up to 100 times more potent in vitro than the racetam aniracetam at the same job. Rather than becoming a drug candidate, it became a reference tool; its unusual preference for GluA3 and GluA4 subunits let scientists map receptor subtype pharmacology in ways cruder compounds couldn't. It did show real translational promise, improving memory in rats after ischemic brain injury when given systemically, but no pharmaceutical company appears to have picked it up for clinical development. It remains, decades later, mostly a lab reagent rather than a museum piece with a failed-trial story; a compound whose whole career happened on the bench.
PF-04958242 was Pfizer's AMPA receptor potentiator, and unusually for this drug class it actually cleared a real human test: in a 2017 study, healthy volunteers were given ketamine to induce NMDA-hypofunction cognitive deficits (a validated schizophrenia-like model), and PF-04958242 measurably protected their verbal learning, recall, and working memory performance against the ketamine hit. That's about as close as any ampakine has come to proving the concept works in people. Pfizer nonetheless terminated its own Phase 2 trial in 2016 during an internal portfolio prioritization, not because of a safety or efficacy failure. Biogen then acquired the asset in 2018, calling it a first-in-class, Phase 2b-ready compound, renamed it BIIB104, and pushed it into further cognitive-impairment-in-schizophrenia (CIAS) trials into the early 2020s. As of the mid-2020s it has not emerged as an approved product and appears to have stalled again.
PF-04995274 is a selective, brain-penetrant 5-HT4 receptor partial agonist originally developed by Pfizer that has become the leading clinical probe for pro-cognitive and antidepressant effects of central 5-HT4 activation in humans. It advanced into experimental medicine studies in major depressive disorder, where short courses altered emotional and memory-related brain circuitry in ways distinct from a conventional selective serotonin reuptake inhibitor. In the RESTAND programme it increased hippocampal and parietal activity during memory encoding and produced early signals of mood improvement without the classic negative-bias shift seen with citalopram. It remains an investigational compound and is not approved for any indication.
PF-06827443 is a Pfizer M1-selective positive allosteric modulator designed to test whether M1 modulation without agonist activity could avoid cholinergic toxicity; it produced cholinergic adverse events and convulsions in animals anyway.
Pitolisant is a histamine H3 receptor antagonist and inverse agonist used to treat excessive daytime sleepiness and cataplexy in adults with narcolepsy. By blocking the H3 autoreceptor it boosts the brain's own histamine signalling, which promotes wakefulness and places it among the wake-promoting agents sometimes called eugeroics. Marketed mainly as Wakix, it was approved in the European Union in 2016 and by the United States FDA in 2019, and it is unusual among narcolepsy drugs in not being classified as a controlled substance in the United States.
PNU-120596 is a selective type II positive allosteric modulator of the alpha7 nicotinic acetylcholine receptor; it raises channel open probability and destabilizes receptor desensitization to amplify cholinergic signaling without directly activating the receptor. It is an investigational research tool used to probe alpha7 mechanisms in cognition, schizophrenia and inflammation, and is not approved for human use.
Pomaglumetad methionil (developmental code LY2140023) is the methionine amide prodrug of LY404039, a selective orthosteric agonist of group II metabotropic glutamate receptors (mGlu2 and mGlu3). Developed by Eli Lilly, it represented a bold attempt to treat schizophrenia by normalizing glutamate rather than blocking dopamine. An early phase 2 trial reported antipsychotic efficacy comparable to olanzapine without the weight gain, prolactin elevation or extrapyramidal effects of dopamine antagonists, but larger confirmatory trials failed to replicate the benefit. Pomaglumetad is a landmark case study in glutamatergic antipsychotic development and the challenges of reproducing early proof-of-concept results.
A selective M1 positive allosteric modulator from Merck, used as the reference preclinical tool for the claim that boosting acetylcholine at M1 alone improves cognition without the gut effects of a cholinesterase inhibitor.
Pregnenolone sulfate (PregS) is an endogenous excitatory neurosteroid (a steroid synthesized in and acting upon the nervous system) formed by sulfation of pregnenolone at its 3beta-hydroxyl group. It is among the most intensively studied neurosteroids in ion-channel pharmacology, acting simultaneously as a positive allosteric modulator of N-methyl-D-aspartate (NMDA) receptors that contain GluN2A or GluN2B subunits (the principal glutamate-gated channels underlying synaptic plasticity), a negative allosteric modulator of GABA-A receptors (the brain's main inhibitory chloride channels), a low-affinity agonist of the sigma-1 receptor (an intracellular chaperone protein) and the prototypical agonist of the TRPM3 cation channel. Through these convergent actions it enhances glutamatergic transmission, hippocampal acetylcholine release, long-term potentiation and memory consolidation in animal models, which underlies its reputation as a pro-cognitive neurosteroid. Its physiological concentrations, and even its unambiguous presence in mammalian brain, remain debated, so much of the evidence base derives from experimental administration rather than demonstrated endogenous signaling.
Propentofylline was developed by the German pharmaceutical company Hoechst under the code HWA 285 as a glia-targeting approach to dementia, a methylxanthine derivative that inhibits adenosine reuptake and calms overactive microglia, on the theory that quieting neuroinflammation could slow neurodegeneration even without directly boosting neurotransmission. It advanced all the way to Phase III trials in Europe and North America during the 1990s for Alzheimer's disease and vascular dementia, and showed modest positive signals in some vascular-dementia cohorts, but it never delivered a clean enough efficacy result across trials to win broad approval and was ultimately discontinued, though it stayed available a while longer in a few markets such as Canada. It remains referenced in neuroinflammation research as one of the earlier serious attempts to treat dementia by targeting glial cells rather than neurons directly.
A Pfizer M1 positive allosteric modulator whose tritiated form became the first radioligand for the M1 allosteric site, letting a program rank modulators by how tightly they bind instead of only by what they do.
R13 is a prodrug of 7,8-dihydroxyflavone, built by capping both of the parent compound's hydroxyl groups with carbamate esters so it survives the gut better. It was the one candidate out of twenty screened derivatives that made it through to animal work. It roughly doubles oral bioavailability and half-life compared with the parent, and in Alzheimer's model mice it reduced amyloid deposition, protected synapses and improved maze performance. ⚠️ Its mechanism inherits an argument. R13 is assumed to work by releasing 7,8-dihydroxyflavone, which is assumed to activate the TrkB receptor, and that second assumption is contested, with independent groups having failed to reproduce receptor activation.
R7 is a 7,8-dihydroxyflavone derivative that appears in research-chemical channels as a prodrug of that compound. ⚠️ It is a rejected candidate, and that is essentially the whole entry. R7 was one of twenty derivatives screened in a 2018 study, and it was eliminated before any animal work for a specific reason: it barely released 7,8-dihydroxyflavone in human liver preparations. A sibling from the same screen, R13, was the one that advanced. That single sentence is the entire published literature on R7. There is no structure, no formula, no measured affinity for anything, no animal study, no pharmacokinetics and no safety data.
Rapastinel (originally GLYX-13) is a tiny four-amino-acid peptide (Thr-Pro-Pro-Thr with an amidated tail) that acts as a functional partial agonist at the glycine site of the NMDA receptor. It was the lead candidate in the wave of rapid-acting antidepressants inspired by ketamine, meant to lift mood within a day without ketamine's dissociation; it looked promising through phase 2 but failed its phase 3 depression trials in 2019.
Roflumilast is a selective PDE4 inhibitor approved as a once-daily oral anti-inflammatory for severe COPD (Daliresp, Daxas) and as a topical treatment for psoriasis and other skin conditions (Zoryve). By blocking PDE4 it raises intracellular cAMP, calming inflammatory cells and, in the brain, boosting the CREB-to-BDNF signaling tied to learning and memory. That neuro angle has turned low, sub-emetic microdoses of roughly 100-250 micrograms into a genuinely intriguing but still preliminary nootropic candidate.
Rolipram (ZK 62711) is the prototypical PDE4 inhibitor and the reference compound for the entire class. Developed by Schering as an antidepressant in the 1980s, it was abandoned over severe emesis but went on to become the single most-studied molecule in the cAMP/CREB-enhances-memory literature. It reliably converts early- to late-long-term potentiation and rescues memory across Alzheimer, aging and Rubinstein-Taybi models, making it the yardstick every newer PDE4 memory drug is measured against.
Rolziracetam was developed as CI-911 during the 1980s racetam research wave that piracetam's success touched off across European and American pharma chemistry, one of many cyclic-imide/pyrrolidinone analogs screened for "amnesia-reversal" activity against scopolamine-induced memory deficits in rodents, the field's standard nootropic assay at the time. It performed in that classic screening model and had its metabolic disposition characterized in animal studies, but like most second-generation racetams it never accumulated the human efficacy data needed to reach market. The entire racetam class shared the same problem: a diffuse, hard-to-pin-down mechanism that made regulatory approval an uphill argument, and once the pharmaceutical industry's attention moved to more mechanistically defined drug classes, compounds like rolziracetam simply stopped being worth developing further.
RS-67333 is a selective, high-affinity partial agonist of the serotonin 5-HT4 receptor that has become the reference pharmacological tool for probing the pro-cognitive and disease-modifying potential of 5-HT4 activation in the central nervous system. Unlike the marketed gastrointestinal 5-HT4 agonists, RS-67333 crosses the blood-brain barrier readily and has been studied almost exclusively in preclinical models of learning, memory, and Alzheimer's disease. Its signature finding is that chronic 5-HT4 stimulation shifts amyloid precursor protein processing toward the non-amyloidogenic alpha-secretase pathway, increasing release of the neurotrophic sAPPalpha fragment while lowering amyloid-beta. RS-67333 is an investigational research compound with no human clinical development and no approved use.
Servier, the French pharmaceutical company, developed S 38093 as a histamine H3 receptor antagonist meant to work alongside existing Alzheimer's drugs rather than replace them, stimulating hippocampal neurogenesis and boosting acetylcholine release in a way that looked synergistic with donepezil in aged-mouse models. That preclinical promise carried it into two large international Phase II programs, one alone and one combined with donepezil, enrolling more than 1,300 patients with mild-to-moderate Alzheimer's disease across roughly 40 countries. After a year of dosing at three different levels, none of the arms beat placebo on cognition, function, clinical global impression, or caregiver burden, and treated patients had more falls than those on placebo; Servier discontinued the program on efficacy grounds despite the drug being otherwise reasonably well tolerated.
S-18986 was French pharmaceutical company Servier's entry into the ampakine race, developed through the 2000s as a cognitive enhancer aimed squarely at age-related memory decline and Alzheimer's disease. The preclinical dossier was genuinely broad, covering procedural, spatial, episodic, working, and relational memory tasks in both young-adult and aged rodents, plus measurable increases in hippocampal BDNF and reduced oxidative stress markers in old rats. But like nearly every AMPA potentiator before it, the leap from rodent memory tasks to convincing human cognitive data never happened; a review co-authored by Servier's own researchers in 2010 candidly noted that no AMPA potentiator had yet demonstrated real clinical efficacy. S-18986 faded out of the literature not long after, without a publicized trial failure, just a quiet stop.
Sabcomeline was SmithKline Beecham's most clinically advanced muscarinic-agonist candidate for Alzheimer's disease, marketed in development under the name Memric, and it made it further than most of its rivals in this slice, all the way to Phase III. It bound all five muscarinic receptor subtypes with similar raw affinity but showed functional selectivity for M1 in both cell assays and animal behavior, reversing delay-induced memory deficits in marmosets and rats at doses well below those that triggered cholinergic side effects. Despite genuinely promising early signals of symptomatic benefit in Alzheimer's patients without provoking overt cholinergic toxicity, the Phase III program ultimately produced disappointing results and SmithKline Beecham shelved it, one more entry in the long list of muscarinic-agonist Alzheimer's drugs that looked good on paper and in monkeys but not in a pivotal trial.
Sabeluzole (R 58 735) is a benzothiazole derivative developed by Janssen Pharmaceutica as a neuroprotective memory enhancer. In controlled studies it improved learning and recall in healthy elderly volunteers and showed signs of stabilizing cognition in Alzheimer's disease over a year of treatment. Its actions are attributed to modulation of sodium channels, protection against glutamate excitotoxicity and anoxia, and effects on fast axonal transport. Development was ultimately discontinued, but it remains a notable historical cognition-focused neuroprotectant.
Dalzanemdor (SAGE-718) is a first-in-class, orally administered synthetic neuroactive steroid developed by Sage Therapeutics that acts as a positive allosteric modulator (a molecule that boosts a receptor's response without occupying its main agonist site) of the N-methyl-D-aspartate (NMDA) receptor, the principal excitatory glutamate-gated ion channel of the brain. It is a structural analog of the endogenous brain oxysterol 24(S)-hydroxycholesterol (24(S)-HC), a cholesterol metabolite that the same laboratory identified as a naturally occurring NMDA receptor PAM. The compound was advanced into clinical development for cognitive impairment associated with disorders thought to involve NMDA receptor hypofunction, including Huntington's disease, Parkinson's disease, and Alzheimer's disease. Its Phase 2 program, most notably the DIMENSION study in Huntington's disease, largely failed to meet primary cognitive endpoints during 2024 and 2025, after which Sage Therapeutics terminated the open-label Phase 3 PURVIEW study.
Sapunifiram (MN-19) is an investigational piperidine cognition-enhancer developed by the medicinal chemistry group at the University of Florence as a close structural relative of sunifiram (DM235). Like its parent scaffold, it produces potent antiamnesic and procognitive effects in rodent avoidance paradigms at very low doses, with reported potency exceeding that of piracetam. It is best understood as an ampakine-like glutamatergic and cholinergic facilitator rather than a classical racetam, and it has never advanced beyond preclinical characterization. It remains a purely research-grade compound of interest to structure-activity chemists and the nootropic community.
SB-271046 is one of the first potent and selective serotonin 5-HT6 receptor antagonists, developed at SmithKline Beecham as a research tool and early cognition-enhancer candidate. It is a benzothiophene sulfonamide with high 5-HT6 affinity and behaves as an antagonist or inverse agonist at the receptor. Widely used in preclinical neuroscience, it helped establish the link between 5-HT6 blockade and increased cortical glutamate and cognitive performance. It was never developed into a marketed drug and remains a benchmark reference antagonist for the receptor.
SB-399885 is a potent, selective and orally active serotonin 5-HT6 receptor antagonist developed at GlaxoSmithKline as a cognition-enhancer research compound. It has very high 5-HT6 affinity and more than 200-fold selectivity over other receptors, ion channels and enzymes, making it one of the cleaner pharmacological probes for the receptor. In rodent studies it reversed scopolamine- and dizocilpine-induced memory deficits, improved spatial learning in aged rats and raised cortical acetylcholine. It was never marketed but is a well-validated tool antagonist widely used to test the 5-HT6 cognition hypothesis.
Sialic acid is the common name for a family of nine-carbon acidic sugars, the most abundant of which in humans is N-acetylneuraminic acid (Neu5Ac). These monosaccharides sit at the outer ends of the sugar chains that coat cell surfaces and many secreted proteins, where they take part in cell recognition, immune regulation, and nervous system function. Sialic acid is especially concentrated in the brain and is also present in human milk.
SKF-38393 is a synthetic organic compound of the benzazepine class that acts as a selective agonist at the dopamine D1 receptor family. It is not a medicine but a research chemical, used in laboratory and animal studies to probe the functions of D1-type dopamine receptors. Because it stimulates these receptors relatively selectively, it has served as a standard tool for investigating dopamine signaling in the brain.
SL65.0155 is a selective 5-HT4 receptor partial agonist developed as a cognition-enhancing candidate, notable for producing robust improvements in learning, memory, and attention in rodents at very low doses. It reversed associative learning deficits after hippocampal damage and enhanced attentional performance comparable to nicotine in the five-choice serial reaction time task. Alongside RS-67333, it is one of the classic experimental 5-HT4 agonists used to establish the receptor as a pro-cognitive and potential anti-dementia target. SL65.0155 is an investigational research compound without approved use.
Solriamfetol is an oral selective dopamine and norepinephrine reuptake inhibitor (a phenylalanine derivative) approved in the United States and European Union to improve wakefulness in adults with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea. It is marketed as Sunosi and is a US Schedule IV controlled substance.
Souvenaid is a medical food, taken as a once-daily nutritional drink, that is intended to support the formation of synapses in people with early Alzheimer's disease. It contains a patented mixture of nutrients called Fortasyn Connect, combining omega-3 fatty acids, uridine monophosphate, choline, phospholipids, and several vitamins. Clinical trials have produced mixed results, and systematic reviews have found little convincing effect on cognitive decline, although the product is generally well tolerated.
Suritozole took the opposite approach from a sleeping pill; instead of boosting GABA-A signaling like a benzodiazepine, Marion Merrell Dow (via the MDL research code) built it as a partial inverse agonist at the benzodiazepine site, a molecule meant to dial GABA-A activity down just enough to sharpen memory and arousal without tipping into the anxiety or seizures that full inverse agonists cause. It moved into clinical evaluation for both depression and Alzheimer's-related memory loss in the 1990s, backed by animal data showing it could blunt cognitive impairment after traumatic brain injury in rats. The clinical program quietly stopped without ever producing published efficacy results, leaving it as a research reagent rather than a medicine.
A Takeda M1 positive allosteric modulator built deliberately weak at amplifying acetylcholine, made to test whether a low cooperativity ceiling is what separates a procognitive effect from cholinergic side effects.
T-588 came out of Toyama Chemical in Japan as a multi-target cognitive enhancer built for the vascular-dementia and post-stroke cognitive-impairment niche that Japanese pharma researched heavily in the 1990s, a market segment Western companies mostly ignored. Rather than hitting one clean receptor, it increased acetylcholine and noradrenaline release in the cortex and hippocampus, blocked an outward potassium current in CA1 neurons, and protected cerebellar granule cells from glutamate excitotoxicity, a genuinely broad-spectrum profile aimed at both boosting transmission and shielding neurons from ischemic damage. It compensated for scopolamine-induced learning impairment and improved working memory after simulated cerebral ischemia in rodents, but like most Japanese vascular-cognition compounds of its era, it never crossed into Western regulatory pipelines and faded from view once academic interest moved to other neuroprotective targets.
T-817MA, later given the generic name edonerpic maleate, was developed by Toyama Chemical (subsequently absorbed into Fujifilm's pharmaceutical division) as a neurotrophic and neuroprotective small molecule aimed squarely at Alzheimer's disease, but built on a different premise than amyloid-clearing antibodies: promote neurite outgrowth and protect synapses from amyloid-beta toxicity directly. It advanced through multiple Phase II trials in Japan, the US and Europe, including a joint program with the Alzheimer's Disease Cooperative Study, and produced a real biomarker signal, dose-dependent drops in cerebrospinal fluid tau. That biomarker success never translated into a clinical cognitive benefit large enough to justify a Phase III program, and the compound was shelved, joining the long list of tau- and neuroprotection-targeted Alzheimer's candidates that moved the numbers without moving the patient.
A Takeda M1 positive allosteric modulator aimed at constipation rather than cognition; it amplifies the enteric nervous system's own acetylcholine signaling to produce coordinated, propagating colonic contractions.
Tabernanthalog (TBG) is a synthetic analogue of the plant alkaloid ibogaine, engineered to be water-soluble and, according to its developers, non-hallucinogenic and less toxic than the parent compound. It was created in the laboratory of David Olson at the University of California, Davis, as an example of a psychoplastogen, a molecule meant to promote the rewiring of brain circuits. In rodent studies it has shown antidepressant-like effects and has reduced alcohol- and drug-seeking behavior without triggering the responses that signal a psychedelic experience.
Tacrine earns its spot in this archive on historical weight rather than obscurity; it was the first drug the FDA ever approved for Alzheimer's disease, launched in 1993 under the name Cognex and proof-of-concept that the cholinergic hypothesis (that boosting acetylcholine could meaningfully help Alzheimer's symptoms) actually worked in the clinic, opening the door for donepezil, rivastigmine, and galantamine to follow. That legacy came with a real cost; tacrine caused liver-enzyme elevations in roughly a quarter to half of treated patients, serious enough that trial protocols required stopping the drug if ALT rose above three times normal, and while the injury was almost always reversible on discontinuation, the burden of mandatory liver monitoring made tacrine impractical once safer, twice-a-day alternatives without the hepatotoxicity reached the market. Its manufacturer discontinued marketing tacrine in the United States in 2013, quietly retiring the drug that had started the entire cholinesterase-inhibitor era.
Balipodect (TAK-063) is a selective phosphodiesterase 10A (PDE10A) inhibitor developed by Takeda as a potential antipsychotic for schizophrenia. It has completed phase 2 proof-of-concept testing and, as of 2026, was acquired by Axsome Therapeutics for further development.
TAK-071 is Takeda's M1 muscarinic positive allosteric modulator, built around a deliberately low cooperativity value on the finding that cooperativity, not potency, is what decides whether an M1 drug causes diarrhoea; it reached a phase 2 crossover trial in Parkinson disease where it missed its gait endpoint and improved a secondary cognitive measure.
TAK-137; the preclinical low-agonism AMPA receptor potentiator that pioneered the wide-seizure-margin design later carried into the clinical lead TAK-653, with strong procognitive animal data but no human efficacy program.
TAK-418; a brain-penetrant LSD1/KDM1A epigenetic inhibitor for neurodevelopmental disorders that re-normalizes dysregulated gene expression while sparing the blood toxicity of earlier LSD1 drugs; clean phase 1, efficacy unproven.
luvadaxistat (TAK-831 / NBI-1065844); a selective DAAO inhibitor that raises D-serine to enhance NMDA-receptor co-agonism for schizophrenia cognition, with strong preclinical plasticity data but underwhelming phase 2 results.
Talsaclidine is a functionally M1-preferring muscarinic agonist developed by Boehringer Ingelheim for Alzheimer's disease; it lowered cerebrospinal fluid amyloid beta in patients but hit dose-limiting sweating and hypersalivation before it reached procognitive doses.
Tau peptide is a loosely used name for short peptide preparations marketed for brain and cognitive support, usually grouped with so-called bioregulator peptides. The label is not well standardized, and the sequences sold under it vary between vendors, so the name says little about the precise contents of a given product. Any connection to tau, the microtubule-associated protein of the nervous system, is largely nominal, and rigorous human data are scarce.
TC-5619 was Targacept's alpha7 nicotinic acetylcholine receptor partial agonist, one of the most closely watched compounds of the alpha7-for-schizophrenia wave that swept through pharma in the early 2010s. An initial exploratory Phase II trial, run as an add-on to quetiapine or risperidone in schizophrenia outpatients, found statistically significant improvement on both a spatial-learning task (the Groton Maze Learning Task) and negative symptoms (SANS), enough of a signal that Targacept and its partner AstraZeneca pushed forward into a much larger, 477-patient, six-country Phase II trial. That bigger confirmatory study failed to replicate the earlier benefit, joining ABT-126, AQW051, and encenicline in the broader collapse of the alpha7 nicotinic hypothesis for schizophrenia cognition; AstraZeneca and Targacept discontinued the program not long after, and Targacept itself later folded into Catalyst Biosciences.
tc299423 is an experimental (targacept) small-molecule nicotinic agonist with an alpha6-preferring profile; it activates alpha6beta2* receptors at ec50 ~30-60 nm (about 2.5-fold over alpha4beta2), is orally bioavailable with a clean off-target screen, produces alpha6*-mediated reward in place-preference tests, but did not block nicotine self-administration; a research tool showing small molecules can preferentially target alpha6*, not a medicine.
Teniloxazine (also called sufoxazine or sulfoxazine, development code Y-8894, sold in Japan as Lucelan and Metatone) is a morpholine derivative developed by Yoshitomi Pharmaceutical Industries. It acts mainly as a selective norepinephrine reuptake inhibitor with additional serotonergic receptor antagonism [1]. Screened in the mid-1980s as a cerebral activator for cerebrovascular insufficiency and post-stroke sequelae, it was eventually brought to market in Japan as an antidepressant, a marketing status documented outside the primary literature cited here. The published record is thin; most of the primary evidence is small Japanese animal and healthy-volunteer studies from the 1980s, and there is essentially no modern controlled trial data in the English literature.
Theophylline is a naturally occurring methylxanthine (1,3-dimethylxanthine) that has been used as a bronchodilator and respiratory stimulant for more than 80 years. Structurally related to caffeine and theobromine and found in trace amounts in tea and cocoa, it relaxes airway smooth muscle and stimulates respiration through a combination of non-selective phosphodiesterase inhibition and adenosine receptor antagonism. At the low plasma concentrations achieved with modern sustained-release dosing, it also exerts anti-inflammatory effects by restoring histone deacetylase-2 (HDAC2) activity, a mechanism that can reverse corticosteroid resistance in severe asthma and chronic obstructive pulmonary disease (COPD). Because it has a narrow therapeutic window and numerous drug interactions, it is now generally reserved as an add-on therapy after inhaled agents.
THN102 is an investigational drug combination that pairs the wakefulness-promoting agent modafinil with a low dose of flecainide, a compound that here acts on the brain's glial support cells. It was developed by the company Theranexus on the premise that inhibiting connexin gap junctions in astrocytes strengthens modafinil's effects. It has been studied chiefly for the excessive daytime sleepiness of narcolepsy and is not an approved medicine.
Tisolagiline is an investigational, potent and highly selective reversible inhibitor of the enzyme monoamine oxidase B (MAO-B), studied mainly for neurodegenerative and neuropsychiatric conditions. Developed at the Korea Institute of Science and Technology under the code KDS-2010, it has been evaluated in early clinical trials for Alzheimer's disease and related disorders. Unlike older irreversible MAO-B inhibitors, its reversible binding is intended to avoid the compensatory changes that blunt long-term benefit.
Tolibut is a Russian GABA analogue; phenibut with a methyl group where phenibut has plain phenyl, and baclofen with that methyl in place of baclofen's chlorine [6]. It has been described as analgesic, tranquilising and neuroprotective, and essentially all of that rests on Soviet-era rodent work [2][3]. It is not clear that it was ever approved or used medically, even in Russia.
Tremella fuciformis, commonly called snow fungus or silver ear, is a gelatinous white jelly fungus in the family Tremellaceae, valued as both a food and a traditional remedy in East Asia [1]. It is cultivated widely and used in Chinese and other Asian cuisines, typically in sweet dessert soups, and it is studied for bioactive polysaccharides linked to effects on skin hydration, immunity, and cognition [2][3]. As a food-derived fungus, it is generally treated as a culinary or supplemental ingredient rather than a drug.
Trimethadione is an oxazolidinedione anticonvulsant that was historically used to control absence (petit mal) seizures. It works chiefly by blocking low-threshold T-type calcium channels in thalamic neurons, dampening the rhythmic firing that drives absence seizures. It has largely been replaced by safer drugs and is now mostly of historical and research interest.
Trofinetide is a synthetic analog of the neuroprotective tripeptide glycine-proline-glutamate, the N-terminal fragment of insulin like growth factor 1, and is the first FDA approved treatment for Rett syndrome. It is thought to improve neuronal morphology and synaptic function and reduce neuroinflammation.
Tryptamine is a monoamine alkaloid, an indoleamine built from an indole ring joined to an aminoethyl side chain. It is formed in nature by the decarboxylation of the amino acid tryptophan and serves as the structural parent of a large family of biologically active compounds, including the neurotransmitters serotonin and melatonin, the migraine drugs known as triptans, and psychedelics such as DMT and psilocybin. In the body it occurs at low levels as a trace amine [1].
Tulrampator (S-47445) is a selective positive allosteric modulator of AMPA-type glutamate receptors developed by Servier. Beyond acutely potentiating glutamatergic transmission, it upregulates BDNF and NT-3, activates the mTOR/CREB plasticity pathway, and rescues age-related deficits in hippocampal long-term potentiation and synaptic architecture in animals. It is the best-characterized modern AMPA-PAM and the only ampakine of its cohort to reach large Phase 2 human trials.
Usmarapride is an experimental small-molecule drug that acts as a selective partial agonist of the serotonin 5-HT4 receptor. Developed by Suven Life Sciences under the code SUVN-D4010, it has been studied as a candidate treatment for the cognitive symptoms of Alzheimer's disease and schizophrenia. As of the mid-2020s it had advanced to early-phase clinical testing and is not an approved medicine.
Vasopressin, also called antidiuretic hormone (ADH) or arginine vasopressin, is a peptide hormone made in the hypothalamus and released from the posterior pituitary gland. It helps the body conserve water by concentrating the urine and, at higher levels, narrows blood vessels to raise blood pressure. A manufactured form is used as a medicine in critical care, for example to support blood pressure in shock and to treat certain forms of diabetes insipidus.
Velnacrine is the main liver metabolite of tacrine, and Hoechst-Roussel developed it under the name Mentane hoping that using the metabolite directly, rather than relying on the body to convert tacrine into it, might dodge tacrine's notorious liver-toxicity problem. It did not; clinical trials found the same pattern of asymptomatic but concerning liver-enzyme elevations that had plagued tacrine, and researchers built a statistical risk model (called PROPP) just to try to predict which Alzheimer's patients would develop hepatotoxicity before exposing them to the drug. Hoechst-Roussel ultimately dropped velnacrine after regulators would not approve it on the safety data submitted, a case of a cleaner metabolite turning out to share its parent drug's core problem.
Vesilute is a synthetic dipeptide composed of glutamic acid and aspartic acid (Glu-Asp). It is described as one of the short peptide bioregulators in the tradition of Russian gerontology research and is promoted as a tissue-specific peptide aimed at the urinary tract and bladder. Independent published research on Vesilute itself is very limited, and it is not an approved medicine; it is generally sold and handled as a research peptide.
Vinburnine, also known as eburnamonine, is an indole alkaloid of the eburnamine-vincamine family, related to vincamine and found in plants of the Apocynaceae family. It has been used in some countries as a cerebral vasodilator intended to improve blood flow and oxygen use in the brain, particularly in older adults with cognitive or circulatory complaints. It is chemically related to the better-known compounds vincamine and vinpocetine.
Vincamine is a monoterpenoid indole alkaloid obtained mainly from the leaves of the lesser periwinkle (Vinca minor). It has been used as a cerebral vasodilator to improve blood flow to the brain and is taken for cognitive and cerebrovascular complaints, being available in parts of Europe as a prescription vasodilator and elsewhere as a dietary supplement. It is best known as the parent compound of the semisynthetic derivative vinpocetine.
Vorinostat, also known as suberoylanilide hydroxamic acid or SAHA, is an anticancer drug of the histone deacetylase inhibitor class. In 2006 it became the first histone deacetylase inhibitor approved by the United States Food and Drug Administration, indicated for cutaneous T-cell lymphoma that has persisted or returned after other treatments. It is taken by mouth and works by altering the pattern of chemical marks on chromatin, changing which genes cancer cells express.
VU0467154 is a preclinical positive allosteric modulator of the M4 muscarinic receptor, built at Vanderbilt as an in vivo tool compound, and it is the molecule most of the rodent evidence for the M4 antipsychotic hypothesis actually rests on.
VU0486846 is an experimental M1 muscarinic acetylcholine receptor positive allosteric modulator (an "M1 PAM"; it makes the M1 receptor respond more strongly to the brain's own acetylcholine rather than switching it on directly). It came out of the Vanderbilt neuroscience drug-discovery group and is prized as a "clean" research tool: it improves cognition in animal models without the agonist activity, seizures, and classic cholinergic side effects that plagued earlier M1 activators. It has been studied mostly in models of Alzheimer's disease, schizophrenia-related cognitive deficits, prion neurodegeneration, and Rett syndrome. It is a research compound with no human data.
VU319 is a Vanderbilt-discovered M1-selective positive allosteric modulator with minimal intrinsic agonist activity that completed a first-in-human single ascending dose trial without the cholinergic adverse effects that ended earlier compounds in the class.
WAY-181187 is a potent and selective serotonin 5-HT6 receptor agonist developed at Wyeth as a pharmacological tool to probe the receptor's biology. It is notable for illustrating the 5-HT6 paradox, in which receptor activation, not just blockade, can produce potentially beneficial central effects. In rodents it robustly increases extracellular GABA in cortex, hippocampus, striatum and amygdala, modestly lowers cortical dopamine and serotonin, and attenuates stimulated glutamate. It has shown anxiolytic-like and anticompulsive activity in animal models and is a standard reference agonist for the receptor.
Xaliproden (SR57746A) is a synthetic 5-HT1A serotonin receptor agonist that also shows neurotrophic, NGF-like activity (nerve growth factor supports the survival and repair of neurons). It was investigated as a possible neuroprotective drug in amyotrophic lateral sclerosis (ALS), Alzheimer's disease, and chemotherapy-induced peripheral neuropathy. Trials showed modest signals but it was not approved for these uses.
An M1/M4-preferring muscarinic agonist that failed as an Alzheimer's drug in the 1990s and returned in 2024 as the active antipsychotic half of Cobenfy, the first schizophrenia treatment approved without dopamine receptor blockade.
Xelstrym is dextroamphetamine delivered through the skin, and it is the first amphetamine patch approved for ADHD; the methylphenidate patch preceded it by fifteen years. The drug is not new and nothing about its pharmacology is: what is new is the delivery. A patch worn for about nine hours produces a gradual rise and then a controlled stop when it comes off, which solves two specific problems that oral stimulants handle badly, namely swallowing difficulty and the need to end the effect early rather than wait it out [2]. It was approved in 2022 on the strength of a pivotal study in children and adolescents [1].
Fingolimod is a sphingosine-1-phosphate receptor modulator used to treat relapsing forms of multiple sclerosis. Approved in 2010 and sold as Gilenya, it was the first oral disease-modifying therapy for the condition, offering an alternative to injections for many patients. It works by trapping immune cells in the lymph nodes so that fewer of them can reach and attack the brain and spinal cord.
Neotrofin is the brand name for leteprinim potassium (development code AIT-082), a small purine derivative of hypoxanthine that was investigated as a neurotrophic and memory-enhancing agent. Developed by the company NeoTherapeutics, it works indirectly by prompting the brain to make more of its own neurotrophic factors, such as nerve growth factor. It was tested in Alzheimer's disease but the program was discontinued after only modest results, and it never reached approval.
DHED (10-beta,17-beta-dihydroxyestra-1,4-dien-3-one) is an experimental bioprecursor prodrug of the estrogen 17-beta-estradiol that is inert at estrogen receptors until it is converted to the active hormone. Its defining feature is a striking tissue selectivity: a reductase reaction that occurs in nervous tissue regenerates estradiol within the brain and retina after systemic or topical dosing, while the molecule remains unchanged in the periphery, so it does not raise circulating estrogen or stimulate the uterus, breast, or pituitary. In rodent models this brain-restricted delivery has relieved menopausal and androgen-deprivation hot flushes, provided neuroprotection after stroke, and, as eye drops, preserved retinal ganglion cells and visual function in glaucoma models. DHED remains a preclinical agent, but it exemplifies a prodrug strategy aimed at capturing estrogen's central benefits while avoiding the systemic risks that limit conventional hormone therapy.
AF710B, also known as ANAVEX 3-71 (later ANAVEX3-71), is an experimental small-molecule drug that acts as a selective allosteric agonist of the M1 muscarinic acetylcholine receptor and an agonist of the sigma-1 receptor. Originating from the medicinal-chemistry work of Abraham Fisher and developed by Anavex Life Sciences, it has been investigated as a potential disease-modifying treatment for Alzheimer's disease and related neurodegenerative and psychiatric conditions.
