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the sci-wiki/effects/Cognition

Cognition

Every compound in the sci-wiki that affects cognition; the ones you can source are floated to the front, then the reference-only entries. Tap any for the full entry, mechanism, and outlets.

10 sourced · 38 reference

←cognition48/48filter this drawer by compound name

Creatine

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.

N-PEP-12

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.

Paraxanthine

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.

Tropisetron

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.

AC-262536

AC-262536, also written AC-262,536, is a nonsteroidal selective androgen receptor modulator (SARM) first characterized by Acadia Pharmaceuticals. It acts as a partial agonist of the androgen receptor and was studied preclinically for its tissue-selective anabolic profile, producing muscle-building effects while showing comparatively weak activity on reproductive tissue such as the prostate.

Eutropoflavin

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.

Flecainide

Flecainide is a prescription Class Ic antiarrhythmic best known for suppressing ventricular and supraventricular arrhythmias, but it is featured here through an unconventional cognition and neuroprotection lens rather than its approved cardiac indication. The scientific hook is that flecainide, in addition to blocking the cardiac sodium channel, directly stabilizes the ryanodine receptor RyR2 and suppresses pathological intracellular calcium leak; the same RyR2 calcium leak has been implicated in neuronal dysfunction, tau pathology, and cognitive impairment in Alzheimer's models and in heart failure associated cognitive decline. A separate line of work shows that sodium channel blockade with flecainide protects axons from degeneration in neuroinflammatory models, which is a distinct neuroprotective rationale. Some users additionally pair a low dose antiarrhythmic with stimulants used for focus, reasoning that stimulants raise heart rate and arrhythmia risk while flecainide has proven antiarrhythmic action; this pairing is a theoretical, off label rationale rather than an established protocol. It is essential to be clear that human cognitive enhancement evidence for flecainide is preclinical or theoretical, and that flecainide remains a potent cardiac drug with a documented proarrhythmic risk in people with structural heart disease.

Phenylpiracetam Hydrazide

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].

Citicoline + Piracetam

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

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.

reference shelf; no outlet carries these yet

Amphetamine

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

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

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.

Lisdexamfetamine

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

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

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.

(2R,6R)-Hydroxynorketamine

(2R,6R)-Hydroxynorketamine is a downstream metabolite of ketamine, and it is the compound at the centre of the most interesting open question in rapid-acting antidepressant research: whether the mood effect can be separated from the dissociation. In mice, a single dose produces the same antidepressant-like changes as ketamine itself [1], yet at the concentrations that produce them it does not measurably block the NMDA receptor [2]. If that holds, the antidepressant action and the anesthetic, dissociative, abuse-prone action are two different drugs wearing one molecule. The catch is that the behavioural finding has not replicated cleanly, and no human efficacy trial has reported out.

24(S)-Hydroxycholesterol

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.

Alvameline

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.

Arketamine

Arketamine is the R-enantiomer of ketamine, the half that was not developed. It binds the NMDA receptor about four times more weakly than esketamine, and on the standard account that should make it the weaker antidepressant. A large body of rodent work says the opposite: arketamine produces antidepressant-like effects that are more potent and longer lasting, with less dissociation-like behaviour and less abuse-related response [1]. That contradiction made it one of the most anticipated compounds in the field. Then the human trials arrived, and they have not shown an advantage over placebo [2]. It is the clearest example on this site of preclinical promise failing to carry across.

ASP-4345

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

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.

AVN-322

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

AWD 52-39 is an investigational lysergamide (a chemical relative of LSD) that was developed as a nootropic for cognitive disorders before its discontinuation.

Colivelin

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.

Davunetide

Davunetide (NAP; NAPVSIPQ) is an eight-amino-acid peptide derived from activity-dependent neuroprotective protein (ADNP) that stabilizes microtubules and reduces tau pathology, and has been evaluated clinically as an intranasal neuroprotective agent [1][2]. Although early studies suggested cognitive benefit in amnestic mild cognitive impairment and functional improvement in schizophrenia, a large phase 2/3 trial in progressive supranuclear palsy (PSP) found no clinical efficacy [1][3].

DHEA Sulfate

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.

Esketamine

Esketamine is the S-enantiomer of ketamine, the half of the racemic mixture that binds the NMDA receptor several times more tightly, and it is the only member of the ketamine family approved as an antidepressant. As the nasal spray Spravato it is licensed for treatment-resistant depression alongside an oral antidepressant, and for depressive symptoms in adults with active suicidal ideation. Administration is supervised: the dose is taken in a certified setting and the patient is observed for two hours afterwards, because sedation, dissociation and a transient rise in blood pressure are expected rather than rare. It is a real antidepressant with a real effect size and a genuinely inconvenient delivery model.

Etazolate

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.

GSK1034702

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.

HNG (S14G-Humanin)

HNG is a synthetic potency-boosted analog of humanin, a 24-amino-acid peptide encoded within mitochondrial DNA. Swapping one residue (serine to glycine at position 14) makes it roughly a thousand times more cytoprotective than natural humanin in cell assays, which is why almost all animal work on the humanin pathway uses HNG rather than the wild-type peptide. It is studied for protecting neurons against amyloid-beta and ischemic insults, and for metabolic and insulin-sensitizing effects.

HT-0712

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.

Ketamine

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.

Ketone Ester

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].

MIF-1 (Melanostatin)

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.

MK-7622

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.

Muscarinic Toxin 7

A 65 residue three-finger protein from green mamba venom that blocks the M1 muscarinic receptor from an allosteric site; it is the most subtype-selective muscarinic ligand anyone has found.

PF-06827443

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.

Rapastinel

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

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

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.

S107

S107, also called ARM036, is a member of the Rycal class of small molecules that stabilize ryanodine receptors (RyR), the calcium release channels of the sarcoplasmic and endoplasmic reticulum. By preserving the binding of the stabilizing subunit calstabin to leaky RyR channels, S107 reduces pathological intracellular calcium leak implicated in heart failure and arrhythmia [1][2], muscle fatigue and reduced exercise capacity [3], muscular dystrophy [4], and stress-related cognitive dysfunction [5].

Sabcomeline

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.

SAGE-718

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.

TAK-071

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.

Usmarapride

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.

VU0486846

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

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.