WAcamprosate, sold under the brand name Campral, is a medication used along with counselling to treat alcohol dependence.
WAUTEN-67 is an autophagy-enhancing drug candidate that increases autophagic flux in cell lines and in vivo models.
WBenzofuranylpropylaminopentane is a drug with an unusual effects profile. It can loosely be grouped with the stimulant or antidepressant drug families, but its mechanism of action is quite different.
WBNN-20, also known as 17β-spiro-(androst-5-en-17,2'-oxiran)-3β-ol, is a synthetic neurosteroid, "microneurotrophin", and analogue of the endogenous neurosteroid dehydroepiandrosterone (DHEA). It acts as a selective, high-affinity, centrally active agonist of the TrkA, TrkB, and p75NTR, receptors for the neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), as well as for DHEA and DHEA sulfate (DHEA-S). The drug has been suggested as a potential novel treatment for Parkinson's disease and other conditions.
WBNN-27, also known as 17α,20R-epoxypregn-5-ene-3β,21-diol, is a synthetic neurosteroid and "microneurotrophin" and analogue of the endogenous neurosteroid dehydroepiandrosterone (DHEA). It acts as a selective, high-affinity, centrally active agonist of the TrkA and p75NTR, receptors for nerve growth factor (NGF) and other neurotrophins, as well as for DHEA and DHEA sulfate (DHEA-S). BNN-27 has neuroprotective and neurogenic effects and has been suggested as a potential novel treatment for neurodegenerative diseases and brain trauma.
WCatechin is a flavan-3-ol, a type of natural phenol and antioxidant. It is a plant secondary metabolite. It belongs to the group of flavan-3-ols, part of the chemical family of flavonoids.
WCI-966 (developmental code name) is a central nervous system depressant acting as a GABA reuptake inhibitor, specifically a highly potent and selective blocker of the GABA transporter 1 (GAT-1) (IC50 = 0.26 μM), and hence indirect and non-selective GABA receptor full agonist. It was investigated as a potential anticonvulsant, anxiolytic, and neuroprotective therapeutic but was discontinued during clinical development due to the incidence of severe adverse effects at higher doses and hence was never marketed.
WDeoxygedunin, or 14,15-deoxygedunin, is a naturally occurring tetranortriterpenoid isolated from the Indian neem tree, a plant that has been used in India since ancient times as a remedy for various ailments. Deoxygedunin has been found to act as a potent, selective, small-molecule agonist of TrkB, the main receptor of brain-derived neurotrophic factor (BDNF). It produces TrkB-dependent neurotrophic and neuroprotective effects in mice and enhances learning processes. In addition, deoxygedunin evokes rapid TrkB-dependent antidepressant-like effects in the forced swim test, an animal model of depression, similarly to 7,8-dihydroxyflavone (7,8-DHF) and ketamine, and notably with a greater potency than 7,8-DHF. The compound was discovered by the same group that identified 7,8-DHF and N-acetylserotonin as TrkB agonists.
W7,8-Dihydroxyflavone (7,8-DHF) is a naturally occurring flavone found in Godmania aesculifolia, Tridax procumbens, and primula tree leaves. It has been found to act as a potent and selective small-molecule agonist of the tropomyosin receptor kinase B (TrkB), the main signaling receptor of the neurotrophin brain-derived neurotrophic factor (BDNF). 7,8-DHF is both orally bioavailable and able to penetrate the blood–brain barrier. A prodrug of 7,8-DHF with greatly improved potency and pharmacokinetics, R13, is under development for the treatment of Alzheimer's disease.
W4'-Dimethylamino-7,8-dihydroxyflavone (4'-DMA-7,8-DHF) is a synthetic flavone and selective small-molecule agonist of TrkB, the main receptor of brain-derived neurotrophic factor (BDNF), which was derived from structural modification of 7,8-dihydroxyflavone (7,8-DHF). Relative to 7,8-DHF, 4'-DMA-7,8-DHF possesses higher agonistic activity at TrkB, is significantly more potent than 7,8-DHF both in vitro and in vivo, and has a longer duration of action. The compound has been found to produce neuroprotective, neurogenic, and antidepressant-like effects in animals.
WEdaravone, sold as under the brand names Radicava and Radicut among others, is an intravenous medication used to help with recovery following a stroke and to treat amyotrophic lateral sclerosis (ALS).
WEIDD-036, also known as EPRX-036, as well as progesterone 20-oxime (P4-20-O) or 20-(hydroxyimino)pregn-4-en-3-one, is a synthetic, water-soluble analogue of progesterone, a neurosteroid, and the active metabolite of EIDD-1723 (EPRX-01723), a medication developed for the potential treatment of traumatic brain injury.
WEIDD-1723, also known as EPRX-01723 or as progesterone 20E-[O-[(phosphonooxy)methyl]oxime] sodium salt, is a synthetic, water-soluble analogue of progesterone and a neurosteroid which was developed for the potential treatment of traumatic brain injury. It is a rapidly converted prodrug of EIDD-036, which is considered to be the active form of the agent. Previous C3 and C20 oxime derivatives of progesterone, such as P1-185, were also developed and studied prior to EIDD-1723.
WFanapanel, also known as MPQX, is a quinoxalinedione derivative drug which acts as a competitive antagonist of the AMPA receptor. It was under development by Schering AG for the treatment of cerebral ischemia associated with stroke and trauma, but clinical trials were halted for safety reasons related to possible glial cell toxicity and due to intolerable side effects such as excessive sedation, reduction in consciousness, and transient neurological deterioration. The drug was also observed to produce visual alteration and impairment, including blurred vision, strongly impaired color perception, and reduced visual acuity and dark vision, side effects thought to be caused by blockade of AMPA receptors in the retina.
WHIOC is a small-molecule agent which acts as a selective TrkB receptor agonist. It was derived from N-acetylserotonin (NAS). Relative to NAS, HIOC possesses greater potency and a longer half-life. It is described as producing long-lasting activation of the TrkB receptor and downstream signaling kinases associated with the receptor. HIOC is systemically-active and is able to penetrate the blood-brain-barrier. In animal studies, HIOC was found to robustly protect against glutamate-induced excitotoxicity, an action which was TrkB-dependent.
WHomotaurine is a natural amino acid found in seaweed. It is analogous to taurine, but with an extra carbon in its chain. It has GABAergic activity, apparently by mimicking GABA, which it resembles.
WHumanin is a micropeptide encoded in the mitochondrial genome by the 16S ribosomal RNA gene, MT-RNR2. Its structure contains a three-turn α-helix, and no symmetry.
W7β-Hydroxyepiandrosterone (7β-OH-EPIA), also known as 5α-androstan-3β,7β-diol-17-one, is an endogenous androgen, estrogen, and neurosteroid that is produced from dehydroepiandrosterone and epiandrosterone. It has neuroprotective effects and, along with 7α-hydroxyepiandrosterone, may mediate the neuroprotective effects of DHEA. 7β-OH-EPIA may act as a highly potent antagonist of the G protein-coupled estrogen receptor (GPER).
W6-Hydroxymelatonin (6-OHM) is a naturally occurring, endogenous, major active metabolite of melatonin. Similar to melatonin, 6-OHM is a full agonist of the MT1 and MT2 receptors. It is also an antioxidant and neuroprotective, and is even more potent in this regard relative to melatonin.
WIrampanel is a drug which acts as a dual noncompetitive antagonist of the AMPA receptor and neuronal voltage-gated sodium channel blocker. It was under development by Boehringer Ingelheim for the treatment of acute stroke/cerebral ischemia but never completed clinical trials for this indication. Irampanel was also trialed, originally, for the treatment of epilepsy and pain, but these indications, too, were abandoned, and the drug was ultimately never marketed.
WJ147 is an experimental drug with reported effects against both Alzheimer's disease and ageing in mouse models of accelerated aging.
WKaitocephalin is a non-selective ionotropic glutamate receptor antagonist, meaning it blocks the action of the neurotransmitter glutamate. It is produced by the fungus Eupenicillium shearii. Although similar molecules have been produced synthetically, kaitocephalin is the only known naturally occurring glutamate receptor antagonist. There is some evidence that kaitocephalin can protect the brain and central nervous system, so it is said to have neuroprotective properties. Kaitocephalin protects neurons by inhibiting excitotoxicity, a mechanism which causes cell death by overloading neurons with glutamate. Because of this, it is of interest as a potential scaffold for drug development. Drugs based on kaitocephalin may be useful in treating neurological conditions, including Alzheimer's, amyotrophic lateral sclerosis (ALS), and stroke.
WLicostinel (INN) is a competitive, silent antagonist of the glycine site of the NMDA receptor. It was under investigation by Acea Pharmaceuticals as a neuroprotective agent for the treatment of cerebral ischemia associated with stroke and head injuries but was ultimately never marketed. In clinical trials, licostinel did not produce phencyclidine-like psychotomimetic effects at the doses tested, though transient sedation, dizziness, and nausea were observed. In addition to its actions at the NMDA receptor, licostinel also acts as an antagonist of the AMPA and kainate receptors at high concentrations.
WLM22A-4 is a synthetic, selective small-molecule partial agonist of TrkB (EC50 for TrkB activation = 200–500 pM; IC50 for inhibition of BDNF binding to TrkB = 47 nM; IA = ~85%), the main receptor of brain-derived neurotrophic factor. It has been found to possess poor blood-brain-barrier penetration when administered systemically, so LM22A-4 has been given to animals instead via intranasal administration, with central nervous system TrkB activation observed. The compound produces neurogenic and neuroprotective effects in animals, and shows beneficial effects on respiration in animal models of Rett syndrome.
W3β-Methoxypregnenolone, or pregnenolone 3β-methyl ether, also known as 3β-methoxypregn-5-en-20-one, is a synthetic neuroactive steroid and derivative of pregnenolone. It interacts with microtubule-associated protein 2 (MAP2) in a similar manner to pregnenolone and is under development for potential clinical use for indications such as the treatment of brain and spinal cord injury and depressive disorders.
WMinocycline, sold under the brand name Minocin among others, is a tetracycline antibiotic used to treat a number of bacterial infections such as pneumonia. It is generally less preferred than the tetracycline doxycycline. It is also used for the treatment of acne and rheumatoid arthritis. It is taken by mouth or applied to the skin.
WP1-185, also known as progesterone 3-O-(L-valine)-E-oxime or as pregn-4-ene-3,20-dione 3-O-(L-valine)-E-oxime, is a synthetic progestogen and neurosteroid and an oxime ester analogue and prodrug of progesterone. It was developed as an improved water-soluble version of progesterone such that it could be formulated as an aqueous preparation and easily and rapidly administered intravenously as a potential therapy for traumatic brain injury. However, the chemical synthesis of P1-185 was described as somewhat challenging, so oxime conjugates of progesterone of the C20 instead of C3 position, such as EIDD-1723 and EIDD-036, have since been developed.
WProgesterone (P4) is a medication and naturally occurring steroid hormone. It is a progestogen and is used in combination with estrogens mainly in hormone therapy for menopausal symptoms and low sex hormone levels in women. It is also used in women to support pregnancy and fertility and to treat gynecological disorders. Progesterone can be taken by mouth, in through the vagina, and by injection into muscle or fat, among other routes. A progesterone vaginal ring and progesterone intrauterine device used for birth control also exist in some areas of the world.
WR7 is a small-molecule flavonoid and orally active, potent, and selective agonist of the tropomyosin receptor kinase B (TrkB) – the main signaling receptor for the neurotrophin brain-derived neurotrophic factor (BDNF) – which is under development for the treatment of Alzheimer's disease. It is a structural modification and prodrug of 7,8-dihydroxyflavone (7,8-DHF) with improved potency and pharmacokinetics, namely oral bioavailability and duration. R7 was synthesized by the same researchers who were involved in the discovery of 7,8-DHF. A patent was filed for R7 in 2013 and was published in 2015. In 2016, it was reported to be in the preclinical stage of development. R7 was superseded by R13 because while R7 had a good drug profile in animals, it showed almost no conversion into 7,8-DHF in human liver microsomes.
WR13 is a small-molecule flavonoid and orally active, potent, and selective agonist of the tropomyosin receptor kinase B (TrkB) – the main signaling receptor for the neurotrophin brain-derived neurotrophic factor (BDNF) – which is under development for the potential treatment of Alzheimer's disease. It is a structural modification and prodrug of 7,8-dihydroxyflavone (7,8-DHF) with improved potency and pharmacokinetics, namely oral bioavailability and duration. The compound is a replacement for the earlier 7,8-DHF prodrug R7 and has similar properties to it. It was developed because while R7 displayed a good drug profile in animal studies, it showed almost no conversion into 7,8-DHF in human liver microsomes. In contrast to R7, R13 is readily hydrolyzed into 7,8-DHF in human liver microsomes.
WRosin is a glycoside ester of Cinnamyl alcohol and a constituent of Rhodiola rosea.
WSelegiline, also known as L-deprenyl and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. It is provided in the form of a capsule or tablet taken by mouth for Parkinson's disease and as a patch applied to skin for depression.
WSemax is a drug which is used mostly in Russia and Ukraine for a broad range of conditions but predominantly for its purported nootropic, neuroprotective, and neurorestorative properties. Semax has not been evaluated, approved for use, or marketed in other countries such as the United States.
WSimvastatin, sold under the brand name Zocor among others, is a lipid-lowering medication. It is used along with exercise, diet, and weight loss to decrease elevated lipid levels. It is also used to decrease the risk of heart problems in those at high risk. It is taken by mouth.
WTezampanel is a drug originally developed by Eli Lilly which acts as a competitive antagonist of the AMPA and kainate subtypes of the ionotropic glutamate receptor family, with selectivity for the GluR5 subtype of the kainate receptor. It has neuroprotective and anticonvulsant properties, the former of which may, at least in part, occur via blockade of calcium uptake into neurons.
WTolibut, also known as 3-(p-tolyl)-4-aminobutyric acid, is drug that was developed in Russia. It is an analogue of γ-aminobutyric acid (GABA) and is the 4-methyl analogue of phenibut, and is also an analogue of baclofen where the 4-chloro substitution has been replaced with a 4-methyl substitution. Tolibut has been described as possessing analgesic, tranquilizing, and neuroprotective properties. It is not fully clear as to whether the drug was ever approved or used medically in Russia, though it may have been.
W7,8,3′-Trihydroxyflavone (7,8,3'-THF) is a flavone and small-molecule agonist of TrkB, the main receptor of brain-derived neurotrophic factor (BDNF), that was derived from 7,8-dihydroxyflavone (7,8-DHF). Relative to 7,8-DHF, 7,8,3'-THF is 2–3-fold more potent in vitro as a TrkB agonist. 7,3’-Dihydroxyflavone (7,3'-DHF) is also more potent than 7,8-DHF in vitro, indicating that a 3'-hydroxy group on the B-ring enhances TrkB agonistic activity. 7,8,3'-THF has been tested in vivo and was found to produce TrkB-dependent neuroprotective effects in mice similarly to 7,8-DHF.
WZonampanel is a quinoxalinedione derivative drug and competitive antagonist of the AMPA receptor which was being investigated by Yamanouchi/Astellas Pharma as a neuroprotective drug for the treatment of ischemic stroke but never completed clinical trials. In clinical trials, zonampanel produced severe side effects including hallucinations, agitation, and catatonia in patients, resulting in early termination of the trials.