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DS-1 (drug)
DS-1 is a drug from the imidazopyridine family, which is the first drug developed that acts as a GABAA receptor positive allosteric modulator (PAM) selective for the α4 β3 δ subtype, which is not targeted by other GABAA receptor PAMs such as the benzodiazepines or other nonbenzodiazepine drugs. Novel selective drugs such as DS-1 should prove useful in the study of this receptor subtype. See also * Alpidem * Saripidem * Zolpidem Zolpidem, sold under the brand name Ambien, among others, is a medication primarily used for the short-term treatment of sleeping problems. Guidelines recommend that it be used only after cognitive behavioral therapy for insomnia and behavior ... References Benzamides Chloroarenes GABAA receptor positive allosteric modulators Imidazopyridines Organobromides Thiophenes {{sedative-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Imidazopyridine
An imidazopyridine is a nitrogen containing heterocycle that is also a class of drugs that contain this same chemical substructure. In general, they are GABAA receptor agonists, however recently proton pump inhibitors, aromatase inhibitors, NSAIDs and other classes of drugs in this class have been developed as well. Despite usually being similar to them in effect, they are not chemically related to benzodiazepines. As such, GABAA-agonizing imidazopyridines, pyrazolopyrimidines, and cyclopyrrones are sometimes grouped together and referred to as "nonbenzodiazepines." Imidazopyridines include: Sedatives Anxiolytics, sedatives and hypnotics ( GABAA receptor positive allosteric modulators): * Imidazo ,2-ayridines: ** Alpidem (original brand name Ananxyl)—an anxiolytic that was withdrawn from the market worldwide in 1995 due to hepatotoxicity. ** DS-1—a GABAA receptor positive allosteric modulator selective for the α4 β3 δ subtype, which is not targeted by other GABAergic ... [...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] |
Positive Allosteric Modulator
In pharmacology and biochemistry, allosteric modulators are a group of substances that bind to a receptor to change that receptor's response to stimulus. Some of them, like benzodiazepines, are drugs. The site that an allosteric modulator binds to (i.e., an ''allosteric site'') is not the same one to which an endogenous agonist of the receptor would bind (i.e., an ''orthosteric site''). Modulators and agonists can both be called receptor ligands. Allosteric modulators can be 1 of 3 types either: positive, negative or neutral. Positive types increase the response of the receptor by increasing the probability that an agonist will bind to a receptor (i.e. affinity), increasing its ability to activate the receptor (i.e. efficacy), or both. Negative types decrease the agonist affinity and/or efficacy. Neutral types don't affect agonist activity but can stop other modulators from binding to an allosteric site. Some modulators also work as allosteric agonists. The term "allosteric" derive ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
GABRA4
Gamma-aminobutyric acid receptor subunit alpha-4 is a protein that in humans is encoded by the ''GABRA4'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba .... GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA-A receptors, which are ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as benzodiazepines that bind to the GABA-A receptor. At least 16 distinct subunits of GABA-A receptors have been identified. A research study compared wild-type to knockout GABRA4 gene in mice. It was determined that the elimination of the GABRA4 gene displayed characteristics that are associated with autism spectrum disorder (ASD). These include increased spatial cognition and decreased social engagement, un ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
GABRB3
Gamma-aminobutyric acid receptor subunit beta-3 is a protein that in humans is encoded by the ''GABRB3'' gene. It is located within the 15q12 region in the human genome and spans 250kb. This gene includes 10 exons within its coding region. Due to alternative splicing, the gene codes for many protein isoforms, all being subunits in the GABAA receptor, a ligand-gated ion channel. The beta-3 subunit is expressed at different levels within the cerebral cortex, hippocampus, cerebellum, thalamus, olivary body and piriform cortex of the brain at different points of development and maturity. GABRB3 deficiencies are implicated in many human neurodevelopmental disorders and syndromes such as Angelman syndrome, Prader-Willi syndrome, nonsyndromic orofacial clefts, epilepsy and autism. The effects of methaqualone and etomidate are mediated through GABBR3 positive allosteric modulation. Gene The GABRB3 gene is located on the long arm of chromosome 15, within the q12 region in the human genom ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
GABRD
Gamma-aminobutyric acid receptor subunit delta is a protein that in humans is encoded by the ''GABRD'' gene. In the mammalian brain, the delta (δ) subunit forms specific GABAA receptor subtypes by co-assembly leading to δ subunit containing GABAA receptors (δ-GABAA receptors). Structure and function The delta (δ) subunit, one of the subunits of the hetero-pentameric δ-GABAA receptors, is a determinant subunit for the specific cellular localization of δ-GABAA receptors, which are modulated by the GABA. GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts on the repertoire of GABAA receptors, the ligand-gated chloride channels. It is assembled from a diverse subunit pool, including assemblies from a family of 19 subunits (α1-α6, β1-β3, γ1-γ3, δ, ∈, θ, π and ρ1-ρ3). The GABRD gene encodes the delta (δ) subunit. Specifically, the δ-subunit is usually expressed in GABAA receptors associated with extrasynaptic activity, mediating toni ... [...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] |
Nonbenzodiazepine
Nonbenzodiazepines (), sometimes referred to colloquially as Z-drugs (as many of their names begin with the letter "z"), are a class of psychoactive drugs that are very benzodiazepine-like in nature. They are used in the treatment of sleep problems, and for their anxiolytic effects. Nonbenzodiazepine pharmacodynamics are almost entirely the same as benzodiazepine drugs and therefore exhibit similar benefits, side-effects, and risks. However, nonbenzodiazepines have dissimilar or entirely different chemical structures and are therefore unrelated to benzodiazepines on a molecular level. Classes Currently, the major chemical classes of nonbenzodiazepines are: Imidazopyridines * Alpidem * Necopidem * Saripidem * Zolpidem (Ambien, Ambien CR, Intermezzo, Zolpimist, Edluar, Ivadal, Sanval, Stilnox, etc.) Pyrazolopyrimidines * Divaplon * Fasiplon * Indiplon * Lorediplon * Ocinaplon * Panadiplon * Taniplon * Zaleplon (Sonata, Starnoc, Andante) Cyclopyrrolones * Eszopiclone (Lunesta, V ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Alpidem
Alpidem (Ananxyl) is an anxiolytic drug from the imidazopyridine family, related to the more well known sleeping medication zolpidem. Unlike zolpidem however, alpidem does not produce sedative effects at normal doses, and is instead used specifically for the treatment of anxiety. Alpidem was developed by Synthélabo (now part of Sanofi-Aventis). It was approved for marketing in France in 1991. Clinical trials to obtain US FDA approval were halted in 1992 and the drug never received FDA approval. It was withdrawn from the French market by 1994 and is not approved for marketing anywhere in the world. Alpidem has nanomolar binding affinity for both the central benzodiazepine receptor (CBR) and the peripheral benzodiazepine receptor (PBR) (translocator protein 18 kDa) (PBR (Ki ) 0.5-7 nM) and CBR (Ki ) 1-28 nM, respectively). However, the chemical structure of alpidem is not related to that of the benzodiazepines, and alpidem is thus sometimes referred to as a nonbenzodiazepine. ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Saripidem
Saripidem is a sedative and anxiolytic drug in the imidazopyridine family, which is related to the better known drugs zolpidem and alpidem. Saripidem has a similar pharmacological profile to the benzodiazepine family of drugs including sedative and anxiolytic properties, but its chemical structure A chemical structure determination includes a chemist's specifying the molecular geometry and, when feasible and necessary, the electronic structure of the target molecule or other solid. Molecular geometry refers to the spatial arrangement of ... is quite different from that of the benzodiazepine drugs, and saripidem is described as a nonbenzodiazepine. The mechanism of action by which saripidem produces its sedative and anxiolytic effects is by modulating the benzodiazepine binding site on GABAA receptors, however unlike many older GABAA agonists, saripidem is highly subtype selective and binds primarily to the ω1 subtype. References {{GABAAR PAMs Carboxamides ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Zolpidem
Zolpidem, sold under the brand name Ambien, among others, is a medication primarily used for the short-term treatment of sleeping problems. Guidelines recommend that it be used only after cognitive behavioral therapy for insomnia and behavioral changes, such as sleep hygiene, have been tried. It decreases the time to sleep onset by about fifteen minutes and at larger doses helps people stay asleep longer. It is taken by mouth and is available in conventional tablets, sublingual tablets, or oral spray. Common side effects include daytime sleepiness, headache, nausea, and diarrhea. More severe side effects include memory problems and hallucinations. The previously recommended dose was decreased in 2013, by the US Food and Drug Administration (FDA), to the immediate-release 10mg for men, and 5mg for women, in an attempt to reduce next-day somnolence. Newer extended-release formulations include the 6.25mg for women, and 12.5mg or 6.25mg for men, which also cause next-day somnolenc ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Benzamides
Benzamide is a organic compound with the chemical formula of C6H5C(O)NH2. It is the simplest amide derivative of benzoic acid Benzoic acid is a white (or colorless) solid organic compound with the formula , whose structure consists of a benzene ring () with a carboxyl () substituent. It is the simplest aromatic carboxylic acid. The name is derived from gum benzoin, wh .... In powdered form, it appears as a white solid, while in crystalline form, it appears as colourless crystals. It is slightly soluble in water, and soluble in many organic solvents. It is a natural alkaloid found in the herbs of Berberis pruinosa. Chemical derivatives A number of substituted benzamides are commercial drugs, including: See also * References External links Physical characteristics {{Authority control Phenyl compounds ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
