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| Formula | C28H30ClN5O3 |
| Molar mass | 520.03 g·mol−1 |
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Lecozotan is an investigational drug by Wyeth tested for improvement of cognitive functions of Alzheimer's disease patients. [1] As of June 2008 [update] , the first Phase III clinical trial has been completed. [2]
Lecozotan is a competitive, selective 5-HT1A receptor antagonist [3] which enhances the potassium-stimulated release of acetylcholine and glutamate. [4]
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell.
Ampakines, also stylized as AMPAkines, are a subgroup of AMPA receptor positive allosteric modulators with a benzamide or closely related chemical structure. They are also known as "CX compounds". Ampakines take their name from the AMPA receptor (AMPAR), a type of ionotropic glutamate receptor with which the ampakines interact and act as positive allosteric modulators (PAMs) of. Although all ampakines are AMPAR PAMs, not all AMPAR PAMs are ampakines.
A nicotinic agonist is a drug that mimics the action of acetylcholine (ACh) at nicotinic acetylcholine receptors (nAChRs). The nAChR is named for its affinity for nicotine.
The 5HT6 receptor is a subtype of 5HT receptor that binds the endogenous neurotransmitter serotonin (5-hydroxytryptamine, 5HT). It is a G protein-coupled receptor (GPCR) that is coupled to Gs and mediates excitatory neurotransmission. HTR6 denotes the human gene encoding for the receptor.
The alpha-7 nicotinic receptor, also known as the α7 receptor, is a type of nicotinic acetylcholine receptor implicated in long-term memory, consisting entirely of α7 subunits. As with other nicotinic acetylcholine receptors, functional α7 receptors are pentameric [i.e., (α7)5 stoichiometry].
Ispronicline is an experimental drug which acts as a partial agonist at neural nicotinic acetylcholine receptors. It progressed to phase II clinical trials for the treatment of dementia and Alzheimer's disease, but is no longer under development.
Pozanicline is a drug developed by Abbott, that has nootropic and neuroprotective effects. Animal studies suggested it useful for the treatment of ADHD and subsequent human trials have shown ABT-089 to be effective for this application. It binds with high affinity subtype-selective to the α4β2 nicotinic acetylcholine receptors and has partial agonism to the α6β2 subtype, but not the α7 and α3β4 subtypes familiar to nicotine. It has particularly low tendency to cause side effects compared to other drugs in the class, making it an exciting candidate for clinical development.
An H3 receptor antagonist is a classification of drugs used to block the action of histamine at the H3 receptor.
Xanomeline is a small molecule muscarinic acetylcholine receptor agonist that was first synthesized in a collaboration between Eli Lilly and Novo Nordisk as an investigational therapeutic being studied for the treatment of central nervous system disorders.
Neramexane is a drug related to memantine, which acts as an NMDA antagonist and has neuroprotective effects. It is being developed for various possible applications, including treatment of tinnitus, Alzheimer's disease, drug addiction and as an analgesic. Animal studies have also suggested antidepressant and nootropic actions, so there are a wide range of potential applications this drug may be used for. It also acts as a nicotinic acetylcholine receptor antagonist.
SB-271046 is a drug which is used in scientific research. It was one of the first selective 5-HT6 receptor antagonists to be discovered, and was found through high-throughput screening of the SmithKline Beecham Compound Bank using cloned 5-HT6 receptors as a target, with an initial lead compound being developed into SB-271046 through a structure-activity relationship (SAR) study. SB-271046 was found to be potent and selective in vitro and had good oral bioavailability in vivo, but had poor penetration across the blood–brain barrier, so further SAR work was then conducted, which led to improved 5-HT6 antagonists such as SB-357,134 and SB-399,885.
Pomaglumetad (LY-404,039) is an amino acid analog drug that acts as a highly selective agonist for the metabotropic glutamate receptor group II subtypes mGluR2 and mGluR3. Pharmacological research has focused on its potential antipsychotic and anxiolytic effects. Pomaglumetad is intended as a treatment for schizophrenia and other psychotic and anxiety disorders by modulating glutamatergic activity and reducing presynaptic release of glutamate at synapses in limbic and forebrain areas relevant to these disorders. Human studies investigating therapeutic use of pomaglumetad have focused on the prodrug LY-2140023, a methionine amide of pomaglumetad (also called pomaglumetad methionil) since pomaglumetad exhibits low oral absorption and bioavailability in humans.
Sunifiram is an experimental drug which has antiamnesic effects in animal studies and with significantly higher potency than piracetam. Sunifiram is a molecular simplification of unifiram (DM-232). Another analogue is sapunifiram (MN-19). As of 2016, sunifiram had not been subjected to toxicology testing, nor to any human clinical trials, and is not approved for use anywhere in the world.
Altinicline is a drug which acts as an agonist at neural nicotinic acetylcholine receptors with high selectivity for the α4β2 subtype. It stimulates release of dopamine and acetylcholine in the brain in both rodent and primate models, and progressed as far as Phase II clinical trials for Parkinson's disease, where "no antiparkinsonian or cognitive-enhancing effects were demonstrated", although its current status is unclear.
Vabicaserin was a novel antipsychotic and anorectic under development by Wyeth. As of 2010 it is no longer in clinical trials for the treatment of psychosis. It was also under investigation as an antidepressant but this indication appears to have been dropped as well.
Intepirdine (INN; developmental codes SB-742457, RVT-101) is a selective 5-HT6 receptor antagonist with potential cognition, memory, and learning-enhancing effects. It was under development by GlaxoSmithKline for the treatment of Alzheimer's disease and demonstrated some preliminary efficacy in phase II clinical trials. GSK chose not to continue development and sold the rights to Axovant Sciences for $5 million in December 2014.
PRX-07034 is a selective 5-HT6 receptor antagonist. It has cognition and memory-enhancing properties and potently decreases food intake and body weight in rodents. PRX-07034 was under development by Epix Pharmaceuticals for the treatment of obesity and cognitive impairment associated with Alzheimer's disease and schizophrenia but upon the company collapsing due to lack of funds the compound was auctioned to another corporation.
WAY-181187 is a high affinity and selective 5-HT6 receptor full agonist. It induces robust increases in extracellular GABA levels in the frontal cortex, hippocampus, striatum, and amygdala of rats without affecting concentrations in the nucleus accumbens or thalamus, and has modest to no effects on norepinephrine, serotonin, dopamine, or glutamate levels in these areas. WAY-181187 has demonstrated preclinical efficacy in rodent models of depression, anxiety, and notably obsessive-compulsive disorder, though it has also been shown to impair cognition and memory.
Autonomic drugs can either inhibit or enhance the functions of the parasympathetic and sympathetic nervous systems. This type of drug can be used to treat a wide range of diseases, such as glaucoma, asthma, urinary, gastrointestinal and cardiopulmonary disorders.
KarXT is an investigational oral dual-drug fixed-dose combination of xanomeline and trospium which is currently being evaluated in a phase 3 clinical trial for the treatment of patients suffering from the symptoms of schizophrenia. Xanomeline is a functionally preferring muscarinic M4 and M1 receptor agonist that readily passes into the central nervous system (CNS) to stimulate these muscarinic receptor subtypes in key areas of the brain. Trospium is a non-selective muscarinic antagonist that does not cross into the CNS and reduces peripheral cholinergic side effects associated with xanomeline.
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