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GABRA5
Gamma-aminobutyric acid (GABA) A receptor, alpha 5, also known as GABRA5, is a protein which in humans is encoded by the ''GABRA5'' gene. Function gamma-aminobutyric acid, GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABAA receptor, GABAA receptors, which are ligand-gated ion channel, ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as benzodiazepines that bind to the GABAA receptor. At least 16 distinct subunits of GABAA receptors have been identified. Transcript variants utilizing three different alternative non-coding first exons have been described. Subunit selective ligands Recent research has produced several ligands which are moderately selective for GABAA receptors containing the α5 subunit. These have proved to be useful in investigating some of the side effects of benzodiazepine and nonbenzodiazepine drugs, particularly the effects on learning and memory such as anterograde amn ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
GABAA Receptor
The GABAA receptor (GABAAR) is an ionotropic receptor and ligand-gated ion channel. Its endogenous ligand is γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. Upon opening, the GABAA receptor on the postsynaptic cell is selectively permeable to chloride ions (Cl−) and, to a lesser extent, bicarbonate ions (HCO3−). Depending on the membrane potential and the ionic concentration difference, this can result in ionic fluxes across the pore. If the membrane potential is higher than the equilibrium potential (also known as the reversal potential) for chloride ions, when the receptor is activated Cl− will flow into the cell. This causes an inhibitory effect on neurotransmission by diminishing the chance of a successful action potential occurring at the postsynaptic cell. The reversal potential of the GABAA-mediated inhibitory postsynaptic potential (IPSP) in normal solution is −70 mV, contrasting the GABAB IPSP (-100 mV). T ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ligand-gated Ion Channel
Ligand-gated ion channels (LICs, LGIC), also commonly referred to as ionotropic receptors, are a group of transmembrane ion-channel proteins which open to allow ions such as Na+, K+, Ca2+, and/or Cl− to pass through the membrane in response to the binding of a chemical messenger (i.e. a ligand), such as a neurotransmitter. When a presynaptic neuron is excited, it releases a neurotransmitter from vesicles into the synaptic cleft. The neurotransmitter then binds to receptors located on the postsynaptic neuron. If these receptors are ligand-gated ion channels, a resulting conformational change opens the ion channels, which leads to a flow of ions across the cell membrane. This, in turn, results in either a depolarization, for an excitatory receptor response, or a hyperpolarization, for an inhibitory response. These receptor proteins are typically composed of at least two different domains: a transmembrane domain which includes the ion pore, and an extracellular domain wh ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
L-655,708
L-655,708 (FG-8094) is a nootropic drug invented in 1996 by a team working for Merck, Sharp and Dohme, that was the first compound developed which acts as a subtype-selective inverse agonist at the α5 subtype of the benzodiazepine binding site on the GABAA receptor. It acts as an inverse agonist at the α1, α2, α3 and α5 subtypes, but with much higher affinity for α5, and unlike newer α5 inverse agonists such as α5IA, L-655,708 exerts its subtype selectivity purely via higher binding affinity for this receptor subtype, with its efficacy as an inverse agonist being around the same at all the subtypes it binds to. A radiolabelled form of L-655,708 was used to map the distribution of the GABAA α5 subtype in the brain, and it was found to be expressed predominantly in the hippocampus, an area of the brain involved with learning and memory. Activation of this subtype is thought to be largely responsible for producing the cognitive side effects displayed by many benzod ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
SH-053-R-CH3-2′F
SH-053-R-CH3-2′F is a drug used in scientific research which is a benzodiazepine derivative. It produces some of the same effects as other benzodiazepines, but is much more subtype-selective than most other drugs of this class, having high selectivity, binding affinity and efficacy at the α5 subtype of the GABAA receptor. This gives much tighter control of the effects produced, and so while SH-053-R-CH3-2′F retains sedative and anxiolytic effects, it does not cause ataxia at moderate doses. SH-053-R-CH3-2′F also blocks the nootropic effects of the α5-selective inverse agonist PWZ-029, so amnesia is also a likely side effect. Replacement of the ester function by an amide, realized in analogs such as MP-III-022 and GL-II-73 GL-II-73 (GL-ii-073) is a benzodiazepine derivative related in chemical structure to compounds such as midazolam and adinazolam. It is described as an α5 preferring positive allosteric modulator of the benzodiazepine site of GABAA receptors, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Basmisanil
Basmisanil (; developmental codes RG-1662 and RO5186582) is a highly selective inverse agonist/negative allosteric modulator of α5 subunit-containing GABAA receptors which is under development by Roche for the treatment of cognitive impairment associated with Down syndrome. As of June 2016, it is no longer studied. It is studied with schizophrenia patients. See also * List of investigational antipsychotics This is a list of investigational antipsychotics, or antipsychotics that are currently under development for clinical use but are not yet approved. ''Chemical/generic names are listed first, with developmental code names, synonyms, and brand names ... * GABAA receptor negative allosteric modulator * GABAA receptor § Ligands References External links Basmisanil - AdisInsight Fluoroarenes GABAA receptor negative allosteric modulators Nicotinamides Nootropics Isoxazoles {{Nervous-system-drug-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
TB-21007
TB-21007 is a nootropic drug which acts as a subtype-selective inverse agonist at the α5 containing GABAA receptors Receptor may refer to: *Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a n .... See also * GABAA receptor negative allosteric modulator * GABAA receptor § Ligands References Primary alcohols Benzo(c)thiophenes GABAA receptor negative allosteric modulators Ketones Nootropics 2-Thiazolyl compounds Thioethers {{Nervous-system-drug-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Benzodiazepine
Benzodiazepines (BZD, BDZ, BZs), sometimes called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, insomnia, and seizures. The first benzodiazepine, chlordiazepoxide (Librium), was discovered accidentally by Leo Sternbach in 1955 and was made available in 1960 by Hoffmann–La Roche, who soon followed with diazepam (Valium) in 1963. By 1977, benzodiazepines were the most prescribed medications globally; the introduction of selective serotonin reuptake inhibitors (SSRIs), among other factors, decreased rates of prescription, but they remain frequently used worldwide. Benzodiazepines are depressants that enhance the effect of the neurotransmitter gamma-aminobutyric acid (GABA) at the GABAA receptor, resulting in sedative, hypnotic ( sleep-inducing), anxiolytic (anti-anxiety), anticonvulsant, and muscle relaxant properties. High doses o ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ro4938581
Ro4938581 is a nootropic drug invented in 2009 by a team working for Hoffmann-La Roche, which acts as a subtype-selective inverse agonist at the α5 subtype of the benzodiazepine binding site on the GABAA receptor. It has good selectivity for the α5 subtype and did not produce convulsant or anxiogenic effects in animal studies, making it a promising potential nootropic. Ro4938581 and a related derivative basmisanil (RG-1662, RO5186582) have subsequently been investigated for the alleviation of cognitive dysfunction in Down syndrome Down syndrome or Down's syndrome, also known as trisomy 21, is a genetic disorder caused by the presence of all or part of a third copy of chromosome 21. It is usually associated with physical growth delays, mild to moderate intellectual dis .... See also * GABAA receptor negative allosteric modulator * GABAA receptor § Ligands References Imidazobenzodiazepines Triazolobenzodiazepines GABAA receptor negative allosteric mo ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PWZ-029
PWZ-029 is a benzodiazepine derivative drug with nootropic effects developed by WiSys,US Patent application US2006/258643 A1 It acts as a subtype-selective, mixed agonist-inverse agonist at the benzodiazepine binding site on the GABAA receptor, acting as a partial inverse agonist at the α5 subtype and a weak partial agonist at the α3 subtype. This gives it a mixed pharmacological profile, producing at low doses memory-enhancing effects but with no convulsant or anxiogenic effects or muscle weakness, although at higher doses it produces some sedative effects. See also * GABAA receptor negative allosteric modulator * GABAA receptor § Ligands * GL-II-73 GL-II-73 (GL-ii-073) is a benzodiazepine derivative related in chemical structure to compounds such as midazolam and adinazolam. It is described as an α5 preferring positive allosteric modulator of the benzodiazepine site of GABAA receptors, w ... References Chloroarenes Ethers GABAA receptor negative allost ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
QH-ii-066
QH-II-66 (QH-ii-066) is a sedative drug which is a benzodiazepine derivative. It produces some of the same effects as other benzodiazepines, but is much more selective than most other drugs of this class and so produces somewhat less sedation and ataxia than other related drugs such as diazepam and triazolam, although it still retains anticonvulsant effects. QH-ii-066 is a highly subtype-selective GABAA agonist which was designed to bind selectively to the α5 subtype of GABAA receptors. The α5 subtype (and to a lesser extent the α1 subtype) of GABAA are two of the most important targets in the brain that produce the effects of alcohol, and so one of the purposes for which QH-ii-066 was developed was to reproduce the GABAergic effects of alcohol separately from its other actions. QH-ii-066 replicates some of the effects of alcohol, such as sedation and ataxia, but does not increase appetite, as this effect seems to be produced by the α1 subtype of GABAA rather than α5. The ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
α5IA
α5IA (LS-193,268) is a nootropic drug invented in 2004 by a team working for Merck, Sharp and Dohme, which acts as a subtype-selective inverse agonist at the benzodiazepine binding site on the GABAA receptor. It binds to the α1, α2, α3 and α5 subtypes. In Vivo Electrophysiology Recordings of local field potentials Local field potentials (LFP) are transient electrical signals generated in nervous and other tissues by the summed and synchronous electrical activity of the individual cells (e.g. neurons) in that tissue. LFP are "extracellular" signals, meaning ... indicate that oral administration of α5IA increases the amplitude of sharp wave ripples which are implicated in memory function in adult wild type rats. It is intriguing to note that the increase in ripple amplitude is not seen in adult male TgF344-AD rats which express human β-amyloid precursor protein (with the Swedish mutation) and human presenilin-1 (with a Δ exon 9 mutation). See also * GA ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Prader–Willi Syndrome
Prader–Willi syndrome (PWS) is a genetic disorder caused by a loss of function of specific genes on chromosome 15. In newborns, symptoms include weak muscles, poor feeding, and slow development. Beginning in childhood, those affected become constantly hungry, which often leads to obesity and type 2 diabetes. Mild to moderate intellectual impairment and behavioral problems are also typical of the disorder. Often, affected individuals have a narrow forehead, small hands and feet, short height, and light skin and hair. Most are unable to have children. About 74% of cases occur when part of the father's chromosome 15 is deleted. In another 25% of cases, the affected person has two copies of the maternal chromosome 15 from the mother and lacks the paternal copy. As parts of the chromosome from the mother are turned off through imprinting, they end up with no working copies of certain genes. PWS is not generally inherited, but rather the genetic changes happen during the format ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
