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the sci-wiki/effects/Memory

Memory

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

26 sourced · 86 reference

←memory112/112filter this drawer by compound name

Cortexin

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.

Galantamine

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.

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.

Pregnenolone

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

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.

Sabroxy

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.

ISRIB

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.

American Ginseng

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].

Choline Bitartrate

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

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.

DHEA

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.

Ergothioneine

Ergothioneine is a naturally occurring, sulfur-containing amino acid derived from histidine. It is produced only by certain fungi, mycobacteria, and cyanobacteria, yet it accumulates to relatively high levels in animals, including humans, who obtain it entirely from the diet. Mushrooms are the richest common food source. Studied mainly for its antioxidant and cell-protective properties, it is sold as a dietary supplement, although its precise physiological role in humans is not yet firmly established.

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.

FGL

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

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.

Gotu Kola

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.

Hopantenic Acid

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].

Lutein

Lutein is a yellow xanthophyll carotenoid found in dark leafy greens, corn, and egg yolks. In the body it concentrates in the macula of the retina, where together with zeaxanthin it forms the macular pigment, and it is also selectively taken up into the brain by the carrier protein StARD3; macular pigment density has been found to correlate with lutein concentrations in the occipital cortex, so retinal measurements can serve as a non-invasive index of brain lutein. It is studied mainly in relation to eye health and, more tentatively, cognition, and is used as a dietary supplement and, in some regions, as the food colorant E161b.

Nobiletin

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.

Phosphatidylcholine

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.

Piritinol

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.

Rosemary Extract

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.

Vitamin B1 (Thiamine)

Thiamine, also called vitamin B1, is a water-soluble vitamin that acts as an essential coenzyme in carbohydrate and amino acid metabolism. In its active diphosphate form it supports the enzymes that release energy from glucose, and a prolonged dietary shortage produces the deficiency diseases beriberi and Wernicke-Korsakoff syndrome. Thiamine occurs in whole grains, legumes, pork, and nuts, is widely added to fortified flour and rice, and appears on the World Health Organization's list of essential medicines.

Pregnanolone

Pregnanolone (3α-hydroxy-5β-pregnan-20-one, also written 3α,5β-tetrahydroprogesterone) is an endogenous neurosteroid, meaning a steroid that acts rapidly on neuronal ion channels rather than through classical intracellular hormone receptors, formed as a reduced metabolite of progesterone. It is the 5β epimer of allopregnanolone and a potent positive allosteric modulator of the GABA-A receptor (the pentameric chloride channel that carries most fast inhibitory signalling in the brain), giving it sedative, anxiolytic, anticonvulsant and anaesthetic properties. Under the International Nonproprietary Name eltanolone it was developed in the 1990s as an intravenous general anaesthetic, formulated in a soybean-oil emulsion after earlier castor-oil-solubilised steroid anaesthetics proved allergenic; smooth induction and cardiovascular stability were offset by slow recovery and skin reactions, and it was never marketed. Its sulfate and synthetic glutamate esters are studied separately as use-dependent inhibitors of the NMDA receptor, an excitatory glutamate channel implicated in excitotoxicity and neuroprotection.

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

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.

3α-Androstanediol

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.

A4 Amyloid Beta

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.

Adamantyl Carbonyl Proline

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.

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.

Anserine

Anserine is a naturally occurring dipeptide made of beta-alanine and the amino acid 3-methylhistidine, a methylated relative of carnosine. It is found in the skeletal muscle and brain of many animals, especially fish and poultry, though it is present in only small amounts in human tissue. Like carnosine, it acts as an antioxidant and pH buffer, and it is sold as a supplement, usually together with carnosine, and studied mainly for effects on aging and cognition.

Apoaequorin

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.

Arecoline

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.

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.

Bifemelane

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

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.

BnH-015B

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

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.

CAC-253

CAC-253 is the cyclised form of AC253, a 24-residue peptide that BLOCKS the amylin receptor rather than activating it, which makes it the mirror image of the amylin drugs being developed for obesity. It is a preclinical Alzheimer's tool from a single academic laboratory, built on the finding that amyloid beta acts through the amylin receptor [2]. Cyclisation raised its serum half-life from one hour to seven [1]. No human has ever taken it.

Neuroprotection

CAD-31

CAD-31 is a preclinical Alzheimer's candidate from the Salk Institute, selected for its ability to make neural precursor cells divide and then tested in aged Alzheimer's model mice, where it reduced memory deficits and brain inflammation. ⚠️ It has no known molecular target. No binding or potency measurement against any protein has ever been published for it, and its stated mechanism of fatty acid metabolism and inflammation is a description of what changed downstream rather than of what the molecule does. ⚠️ It is frequently grouped with CMS121 as a fisetin derivative. It is not one. Its own paper traces it back through J147 to curcumin, which is different chemistry from a different programme in the same laboratory.

Cebaracetam

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

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].

Cerebroprotein Hydrolysate

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].

CF3CN

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.

Clitoria Ternatea

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].

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.

Convolvulus Pluricaulis

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].

CX-516

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.

Cycloprolylglycine

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.

D-Serine

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.

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].

DHA

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

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.

Dimiracetam

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.

Doliracetam

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.

Dupracetam

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.

Epiandrosterone

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.

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.

Etiracetam

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.

Fosgonimeton

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.

Ginkgolide B

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.

Ginsenoside Rg1

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.

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.

Homotaurine

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.

HTL0018318

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

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.

Indeloxazine

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.

L-Clausenamide

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-Threonic Acid

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.

Methylphenylpiracetam

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].

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.

Milameline

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-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 2

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.

Muscarinic Toxin 3

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.

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.

Myricetin

Myricetin is a naturally occurring flavonoid of the flavonol subclass, a plant pigment found in many fruits, vegetables, berries, teas and wines. Closely related in structure to quercetin, it is studied chiefly for antioxidant and anti-inflammatory activity and a broad range of other effects observed in the laboratory. It is not a drug but a dietary compound, consumed in ordinary foods and sold as a supplement.

Nle1-Angiotensin IV

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.

P7C3

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

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.

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.

PQCA

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.

Neuroprotection

PRE-084

PRE-084 is a synthetic, highly selective agonist of the sigma-1 receptor, an endoplasmic reticulum chaperone protein that modulates calcium signaling, neurotrophic factor expression, and cellular stress responses. It is used almost exclusively as a preclinical research tool, where it has produced neurorestorative effects in models of Parkinson disease [1], motor neuron survival in models of amyotrophic lateral sclerosis [2], and antidepressant and anti-amnesic activity [5]. A recurring theme across studies is upregulation of brain-derived neurotrophic factor (BDNF) and downstream trophic pathways [2][3][4].

Pregnenolone Sulfate

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.

PT-1284

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

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.

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.

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.

Souvenaid

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.

T-495

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.

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.

Talsaclidine

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

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.

Tulrampator

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

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

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.

Vesilute

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.

VU0467154

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

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.

WAY-200070

WAY-200070 is a synthetic nonsteroidal agonist of estrogen receptor beta, made at Wyeth as one of a series designed to tell the two estrogen receptors apart [5]. It binds ERbeta in the low nanomolar range and ERalpha roughly two orders of magnitude more weakly, which is exactly what makes it useful: an effect that appears with WAY-200070 and vanishes in an ERbeta knockout mouse belongs to that receptor rather than to estrogen in general, and that control was actually run [6]. Its reputation in neuroscience comes from hippocampal work, where ERbeta activation raised synaptic proteins and improved memory in rodents [1]. Outside the brain the same compound has been used to study asthma, kidney fibrosis, insulin secretion and cancer cell growth. It is a laboratory probe throughout; there is no approved human use, no human trial, and no human safety data of any kind.

Xanomeline

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.

Zeaxanthin

Zeaxanthin is a yellow-orange xanthophyll carotenoid and one of the most widespread carotenoids in nature. In humans it concentrates with lutein in the macula of the retina to form the macular pigment; at the central fovea, where blue-light exposure and oxidative load are highest, the retina enzymatically converts dietary lutein into a third pigment, meso-zeaxanthin, so that additional protection is generated precisely where it is most needed. Obtained from foods such as corn, peppers, saffron, and goji berries, it is used both as a food coloring and as a dietary supplement studied for eye health, with higher macular pigment density also associated with measures of visual and neural processing.

Fingolimod

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

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

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.