Neurotrophic

9-Me-BC is a β-carboline — the same tryptophan-derived ring system found in cooked meat, coffee and tobacco smoke, and in human blood and brain. Most members of that family damage dopaminergic neurons, which is why they have been investigated as causes of Parkinson's disease; 9-Me-BC does the opposite in cell culture and in one rat study, raising tyrosine hydroxylase, inducing neurotrophic factors and restoring dopamine after a neurotoxin. Ten days of treatment also improved maze learning in rats and thickened dendrites in the dentate gyrus. No human has been studied at any dose.

ACD856 is an experimental oral drug from the Swedish company AlzeCure Pharma. It is a positive allosteric modulator of the Trk receptors: it does not replace BDNF or NGF but makes TrkA, TrkB and TrkC respond more strongly to them. In mice and rats it reversed drug-induced and age-related memory deficits and shortened immobility in the forced swim test. In people it has only been through phase 1: single doses up to 150 mg and seven days at up to 90 mg a day were well tolerated in healthy volunteers, it reached the cerebrospinal fluid, and it shifted the resting EEG, but no published trial has tested whether it improves memory or mood. Every published study comes from the developer.

ARA-290, also called cibinetide, is an 11-amino-acid peptide carved from the three-dimensional structure of erythropoietin - specifically from the face of the molecule that activates tissue repair rather than the face that makes red blood cells. That separation is the whole idea: erythropoietin protects injured tissue in animal models, but raising hematocrit in patients who do not need it causes thrombosis and strokes. ARA-290 has been through several small randomized trials in small fiber neuropathy, where it improved symptoms and increased corneal nerve fiber density, and one in type 2 diabetes where it improved both neuropathic symptoms and HbA1c. The trials are genuinely positive and genuinely small - a few dozen patients each, mostly from one group - and nothing has progressed to a confirmatory phase 3.

BPN14770, now named zatolmilast, is an oral drug candidate from Tetra Therapeutics, a Shionogi subsidiary. It is an allosteric inhibitor of phosphodiesterase-4D (PDE4D), built to raise cAMP signaling in neurons without the vomiting that has stalled other PDE4 inhibitors. In mice carrying the human form of the enzyme it improved memory at oral doses of 0.01–0.03 mg/kg, and a 30-man crossover trial in fragile X syndrome reported gains in language-related cognition. The larger trials have not confirmed it. A 255-patient phase 2 trial in early Alzheimer's disease found no difference from placebo, and in May 2026 Shionogi reported that both phase 3 trials in fragile X syndrome had missed their primary endpoints.

Cerebroprotein hydrolysate is a mixture of low-molecular-weight peptides and amino acids made by enzymatic digestion of pig brain - the same class of product as Cerebrolysin, with which it is used interchangeably in much of the literature. It is licensed and widely prescribed in parts of Asia, Eastern Europe and Latin America for stroke and dementia, and it has been assessed repeatedly by Cochrane. The conclusions are consistent and unflattering. For acute ischemic stroke: across seven RCTs and 1773 participants, no effect on death, and moderate-certainty evidence of an increase in non-fatal serious adverse events (RR 2.39, 95% CI 1.10-5.23). For vascular dementia: cognition and global function improved, but on very low-quality evidence throughout.

Cortagen is the tetrapeptide Ala-Glu-Asp-Pro, the brain-cortex member of the Khavinson family. It has the most concrete animal result in the whole short-peptide program, and it is worth stating precisely: 10 µg/kg intramuscularly for ten days after the sciatic nerve was cut and sutured increased the growth rate of regenerating nerve fibers by 27% and their conduction velocity by 40%. That is a specific dose, a specific model, and two quantified outcomes - which is more than most compounds in this group offer. A follow-up examined delayed effects on injured nerve function, and a microarray study looked at gene expression in mouse heart. The human literature is a Russian-language report of Cortexin and Cortagen in chronic cerebral ischemia.

DNSP-11 is an 11-amino-acid peptide from the pro-domain of GDNF, the glial cell line-derived neurotrophic factor that has been the most persistent hope in Parkinson's disease research. GDNF itself protects and restores dopamine neurons in animals, but it is a large protein that does not cross the blood-brain barrier and has repeatedly disappointed in human trials requiring direct brain infusion. DNSP-11 is an attempt to get the effect from a fragment small enough to deliver differently, and in rats it does have dopamine-neuron-stimulating actions, increases ERK1/2 phosphorylation and works when given intranasally. There is no human study. Notably, it does not appear to act through GDNF's own receptor.

FGL is a synthetic peptide copying the fibroblast growth factor receptor binding site of NCAM, the neural cell adhesion molecule that governs how neurons connect and reconnect. The rodent literature is unusually consistent for a compound in this group: it prevented memory impairment and loss of newborn hippocampal cells after chronic stress in aging animals, rescued spatial learning after neonatal phencyclidine treatment, alleviated amyloid-beta-induced CA1 pyramidal cell loss in young adult rats, mobilized neural stem cells and has an anti-inflammatory action of its own. Those are five separate models pointing the same way. There is still no human trial, and the NCAM-targeting approach has been reviewed as a pharmacological strategy without reaching the clinic.

J147 is a synthetic small molecule from the Salk Institute. It descends from curcumin through a series of hybrid compounds and was chosen because it protected neurons in six different cell models of brain aging. Fed to mice, it improved memory in normal animals, in Alzheimer's-model mice treated late in the disease and in rapidly aging SAMP8 mice. Its target turned out to be the mitochondrial ATP synthase, which it partly inhibits, switching on AMPK. A phase 1 trial in healthy volunteers finished in 2020 and has never reported results, so there is no published human data at any dose.

Noopept is a Russian dipeptide designed to mimic the piracetam pharmacophore, reported active at doses about a thousandth of piracetam's. It is a prodrug: the parent is undetectable in rat brain an hour after dosing, and the active species is cycloprolylglycine, a peptide the brain already makes. Its clinical evidence is Russian, small and uncontrolled, and its primary molecular action appears to be stabilization of HIF-1.

NSI-189 is an investigational benzylpiperazine-aminopyridine selected for neurogenic activity rather than for a known receptor target. A 24-person phase 1b study produced exploratory mood and self-rated cognitive signals, but the 220-person phase 2 trial missed its primary depression endpoint at both 40 and 80 mg a day; some self-rated and CogScreen measures favored 40 mg, while Cogstate did not. Its strongest mechanistic findings remain in cell and rat injury models.

P-21, more precisely written P021, is a tetrapeptide derived from an active region of ciliary neurotrophic factor, with an adamantane group attached to make it stable and brain-penetrant. It comes from Khalid Iqbal's laboratory, and the work is deliberate rather than opportunistic: the founding paper showed the adamantylated peptides improved learning and memory and promoted neurogenesis and synaptic plasticity in mice, and two later studies showed that early treatment prevented amyloid and tau pathology, neurodegeneration and cognitive deficit in mouse models, including when started in early postnatal development. That is a prevention result, which is rarer and harder than rescuing an already-damaged animal. There is no human trial.

Pinealon is a three-amino-acid peptide, Glu-Asp-Arg, from the same St Petersburg program that produced epitalon — designed for the brain rather than the pineal gland despite the name. The cell work is real: it cuts reactive oxygen species and necrotic death in cerebellar granule neurons, neutrophils and PC12 cells, and its labeled form reaches the nucleus and binds DNA sequence-selectively. The animal work is more mixed than the marketing suggests. In old rats given it before carotid occlusion, survival improved but position-finding, motivational behavior and motor performance all fell and brain caspase-3 rose. The one human study — 32 patients, open, Russian-language — found Pinealon less effective than its sister peptide Vesugen, with prooxidant activity on chemiluminescence and a fall in circulating CD34+ cells that the authors read as inhibition of hemopoiesis.

Sabroxy is a branded bark extract of Oroxylum indicum, the Indian trumpet tree. It is standardized to three flavones: oroxylin A, chrysin and baicalein. One 12-week randomized trial in older adults with memory complaints found better episodic memory than placebo. The same trial found no difference on most individual tests, the MoCA or self-rated cognition. That trial is the only controlled human study of the plant.

Semax is a synthetic heptapeptide (Met-Glu-His-Phe-Pro-Gly-Pro), an analog of the ACTH(4-10) fragment of the hormone ACTH, given as a nasal spray. It is used in acute stroke therapy. In rats it raises BDNF and its receptor in the brain. Almost all of its clinical research is published in Russian, and the human studies are small and mostly unblinded.

TAK-653 (osavampator, NBI-1065845) is an AMPA receptor positive allosteric modulator designed to amplify glutamate signaling only where glutamate is already being released — it binds the receptor's ligand-binding domain in a glutamate-dependent way and has virtually no agonist activity of its own, which in rats bought a 419-fold exposure margin against convulsions. In 24 healthy volunteers a single 6 mg dose raised motor-cortex excitability on TMS and produced a mild psychostimulant profile without euphoria or subjective drug effects. A phase 2 trial in depression reported a positive MADRS result, but only in a company press release; two phase 3 trials began in 2025.