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the sci-wiki/effects/BDNF

BDNF

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

3 sourced · 19 reference

←bdnf22/22filter this drawer by compound name

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.

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.

Selank + Semax

Selank + Semax is a nasal spray pairing two Russian research peptides that are normally sold on their own. Selank is a synthetic relative of the immune peptide tuftsin, studied in Russia as an anxiolytic that does not sedate and does not appear to produce the tolerance or withdrawal that benzodiazepines do. Semax is a shortened fragment of ACTH, cut so that it keeps the behavioural effects without the hormonal ones, and studied for attention, stroke recovery and neuroprotection. Both are reported to raise BDNF, and that shared thread is the usual argument for combining them: one takes the edge off, the other sharpens.

reference shelf; no outlet carries these yet

HBT1

HBT1 is a positive allosteric modulator of the AMPA receptor (an "ampakine") that came out of a Takeda drug-discovery program. Its selling point is a gentler profile than earlier ampakines; it has low intrinsic agonist activity and works mostly only when the brain's own glutamate is present, which let it raise BDNF (brain-derived neurotrophic factor, a key growth signal for neurons) in lab neurons without the bell-shaped drop-off and overexcitation that stronger AMPA potentiators tend to cause [1]. It has only been studied in cells and animals, so it remains an experimental research compound rather than an established nootropic.

(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.

ACD856

ACD856 is an experimental drug from the Swedish company AlzeCure Pharma designed to make the brain's own growth factors work harder rather than replacing them; it attaches to the Trk receptors that BDNF and NGF normally act through and amplifies their signal. In animals it improved memory and produced antidepressant-like effects, and in healthy volunteers it was well absorbed, reached the brain, and caused few side effects at single doses up to 150 mg. The evidence stops there; ACD856 has never been tested for effectiveness in anyone with Alzheimer's disease or any other condition, and every published study on it was written by employees of the company that owns it. It is not approved as a medicine anywhere and is currently sold only as a laboratory chemical labelled not for human use.

Alfaxalone

Alfaxalone (also spelled alphaxalone) is a synthetic neuroactive steroid of the pregnane class that produces general anesthesia by acting as a positive allosteric modulator (a molecule that amplifies a receptor's response to its own neurotransmitter) at the GABA-A receptor, the principal inhibitory ion channel of the central nervous system. First introduced in 1971 as the main active component of the intravenous anesthetics Althesin (human) and Saffan (veterinary), it was withdrawn from human use in the 1980s because the solubilizing vehicle Cremophor EL provoked anaphylactoid reactions, then reintroduced in a cyclodextrin formulation marketed for veterinary anesthesia as Alfaxan. Because it lacks classical hormonal activity yet retains rapid, non-cumulative central depressant effects, alfaxalone occupies a distinct pharmacological niche among intravenous anesthetics and now serves as a template for a new generation of water-soluble neurosteroid sedatives such as Phaxan.

Cilomilast

Cilomilast (Ariflo) is a second-generation oral selective PDE4 inhibitor developed by GlaxoSmithKline for COPD and asthma. It reached FDA review but was rejected in 2003-2004 because the respiratory benefit was small and gastrointestinal side effects were dose-limiting. It is not approved anywhere. There is essentially no human cognition data; a single 2025 mouse study reported that cilomilast reversed scopolamine-induced memory deficits through the cAMP/PKA-CREB-BDNF pathway.

Cutamesine

Cutamesine (SA4503) is a selective agonist of the sigma-1 receptor, an endoplasmic reticulum chaperone protein that modulates calcium signaling, mitochondrial function, and multiple neurotransmitter systems. Preclinical work shows that sigma-1 activation enhances neurite and axon outgrowth, protects neurons from oxidative and excitotoxic stress, and improves functional recovery when given days after experimental ischemic stroke, acting through neuroplasticity rather than acute neuroprotection. A phase 2 clinical trial in acute ischemic stroke found cutamesine safe and well tolerated, with a post hoc signal of greater neurological improvement among more severely affected patients. The same sigma-1 mechanism has drawn interest for depression, cognitive impairment, and motor neuron disease, and the carbon-11 labeled compound has been used as a PET radiotracer to quantify sigma-1 receptor occupancy. It has reached human testing but is not an approved drug.

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.

Elunetirom

Elunetirom (ABX-002) is an investigational thyromimetic prodrug designed to deliver selective thyroid hormone receptor beta (TR-beta) activation preferentially to the central nervous system while limiting the systemic thyroid effects that make native thyroid hormone unsuitable as a drug. It belongs to the same CNS-penetrating prodrug class as sobetirome and its amide prodrug Sob-AM2, for which preclinical studies have shown brain-targeted TR-beta engagement that stimulates oligodendrocyte differentiation, promotes myelin repair, and lowers very long chain fatty acids in models of demyelination and X-linked adrenoleukodystrophy. By recreating thyroid hormone action in the brain without body-wide hyperthyroidism, such agents are being explored as add-on treatments for mood disorders and neurological disease. As of the mid-2020s elunetirom remained in clinical trials and had not been approved for any use.

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.

N-Acetyl Selank

N-Acetyl Selank is an acetylated analog of Selank, a synthetic heptapeptide with the sequence Thr-Lys-Pro-Arg-Pro-Gly-Pro that is derived from the immune-modulating peptide tuftsin. Selank was developed at the Institute of Molecular Genetics of the Russian Academy of Sciences and is used in Russia as an anxiolytic and nootropic, typically delivered as a nasal spray. The N-acetyl modification is intended to increase resistance to enzymatic breakdown; it has been studied far less than the parent peptide, and neither form is approved outside a small number of countries.

N-Acetyl Semax

N-Acetyl Semax is an acetylated analog of Semax, a synthetic heptapeptide with the sequence Met-Glu-His-Phe-Pro-Gly-Pro that is based on the ACTH(4-10) fragment of adrenocorticotropic hormone. Developed and studied extensively in Russia, Semax is used there as a nootropic and neuroprotective agent, including in stroke and cognitive disorders, and appears on the Russian list of essential medicines. The N-acetyl modification is meant to improve stability; it is far less studied than the parent peptide, and neither form is approved in most countries.

Neuroprotection

Piclamilast

Piclamilast (RP-73401) is a highly potent, subnanomolar pan-PDE4 inhibitor used mainly as a pharmacological reference tool and high-affinity rolipram-binding-site ligand. It was explored for COPD and asthma but never developed. Its most cognition-relevant finding is a 2022 mouse study in which post-ischemia piclamilast was neuroprotective and preserved memory through CREB, an effect abolished by a CREB inhibitor. There is no human data.

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.

SOMCL-668

SOMCL-668 is the first selective and potent positive allosteric modulator of the sigma-1 receptor, developed by the Shanghai Institute of Materia Medica and characterised at Soochow University. Rather than directly activating the receptor, it amplifies the effects of sigma-1 receptor agonists, and in preclinical models it produces rapid antidepressant, anti-seizure, antipsychotic-like and neuroprotective effects [1][2][3].

TAK-137

TAK-137; the preclinical low-agonism AMPA receptor potentiator that pioneered the wide-seizure-margin design later carried into the clinical lead TAK-653, with strong procognitive animal data but no human efficacy program.

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.

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.