An anxiolytic is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxiety disorders and their related psychological and physical symptoms.
Colloquially known as "downers", depressants or central depressants are drugs that lower neurotransmission levels, or depress or reduce arousal or stimulation in various areas of the brain. Depressants do not change the mood or mental state of others. Stimulants, or "uppers", increase mental or physical function, hence the opposite drug class from depressants are stimulants, not antidepressants.
The GABA receptors are a class of receptors that respond to the neurotransmitter gamma-aminobutyric acid (GABA), the chief inhibitory compound in the mature vertebrate central nervous system. There are two classes of GABA receptors: GABAA and GABAB. GABAA receptors are ligand-gated ion channels ; whereas GABAB receptors are G protein-coupled receptors, also called metabotropic receptors.
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. Accurate regulation of GABAergic transmission through appropriate developmental processes, specificity to neural cell types, and responsiveness to activity is crucial for the proper functioning of nearly all aspects of the central nervous system (CNS). Upon opening, the GABAA receptor on the postsynaptic cell is selectively permeable to chloride ions (Cl−) and, to a lesser extent, bicarbonate ions (HCO3−).
Acamprosate, sold under the brand name Campral, is a medication which reduces alcoholism withdrawal symptoms. It is thought to stabilize chemical signaling in the brain that would otherwise be disrupted by alcohol withdrawal. When used alone, acamprosate is not an effective therapy for alcohol use disorder in most individuals, as it only addresses withdrawal symptoms and not psychological dependence. It facilitates a reduction in alcohol consumption as well as full abstinence when used in combination with psychosocial support or other drugs that address the addictive behavior.
Bretazenil (Ro16-6028) is an imidazopyrrolobenzodiazepine anxiolytic drug which is derived from the benzodiazepine family, and was invented in 1988. It is most closely related in structure to the GABA antagonist flumazenil, although its effects are somewhat different. It is classified as a high-potency benzodiazepine due to its high affinity binding to benzodiazepine binding sites where it acts as a partial agonist. Its profile as a partial agonist and preclinical trial data suggests that it may have a reduced adverse effect profile. In particular bretazenil has been proposed to cause a less strong development of tolerance and withdrawal syndrome. Bretazenil differs from traditional 1,4-benzodiazepines by being a partial agonist and because it binds to α1, α2, α3, α4, α5 and α6 subunit containing GABAA receptor benzodiazepine receptor complexes. 1,4-benzodiazepines bind only to α1, α2, α3 and α5GABAA benzodiazepine receptor complexes.
GABA gamma-aminobutyric acid (GABA) is a key chemical messenger or a neurotransmitter in the central nervous system, that significantly inhibits neuronal transmission. GABA calms the brain and controls several physiological processes, such as stress, anxiety, and sleep. GABAA receptors are a class of ionotropic receptors that are triggered by GABA. They are made up of five subunits that are assembled in various configurations to create distinct receptor subtypes. The direct influx of chloride ions causes rapid inhibitory responses. GABAB receptors are another type of metabotropic receptor that modifies intracellular signaling pathways to provide slower, sustained inhibitory responses. At synapses, GABAA receptors facilitate rapid inhibitory neurotransmission, whereas GABAB receptor which comprise GABA B1 and GABA B2 subunits—control neurotransmitter release and cellular excitability over a longer period of time. These unique qualities help explain the various ways that GABAergic neurotransmission controls brain communication and neuronal function.
A GABA receptor agonist is a drug that is an agonist for one or more of the GABA receptors, producing typically sedative effects, and may also cause other effects such as anxiolytic, anticonvulsant, and muscle relaxant effects. There are three receptors of the gamma-aminobutyric acid. The two receptors GABA-α and GABA-ρ are ion channels that are permeable to chloride ions which reduces neuronal excitability. The GABA-β receptor belongs to the class of G-Protein coupled receptors that inhibit adenylyl cyclase, therefore leading to decreased cyclic adenosine monophosphate (cAMP). GABA-α and GABA-ρ receptors produce sedative and hypnotic effects and have anti-convulsion properties. GABA-β receptors also produce sedative effects. Furthermore, they lead to changes in gene transcription.
Gamma-aminobutyric acid receptor subunit gamma-2 is a protein that in humans is encoded by the GABRG2 gene.
Gamma-aminobutyric acid receptor subunit alpha-1 is a protein that in humans is encoded by the GABRA1 gene.
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.
SL651498 is an anxiolytic and anticonvulsant drug used in scientific research, with a chemical structure most closely related to β-carboline derivatives such as abecarnil and gedocarnil. It has similar effects to benzodiazepine drugs, but is structurally distinct and so is classed as a nonbenzodiazepine anxiolytic.
The GABAA beta-2 subunit is a protein that in humans is encoded by the GABRB2 gene. It combines with other subunits to form the ionotropic GABAA receptors. GABA system is the major inhibitory system in the brain, and its dominant GABAA receptor subtype is composed of α1, β2, and γ2 subunits with the stoichiometry of 2:2:1, which accounts for 43% of all GABAA receptors. Alternative splicing of the GABRB2 gene leads at least to four isoforms, viz. β2-long (β2L) and β2-short. Alternatively spliced variants displayed similar but non-identical electrophysiological properties. GABRB2 is subjected to positive selection and known to be both an alternative splicing and a recombination hotspot; it is regulated via epigenetic regulation including imprinting and gene and promoter methylation GABRB2 has been associated with a number of neuropsychiatric disorders, and found to display altered expression in cancer.
Gamma-aminobutyric acid receptor subunit alpha-6 is a protein that in humans is encoded by the GABRA6 gene.
Gamma-aminobutyric acid receptor subunit alpha-3 is a protein that in humans is encoded by the GABRA3 gene.
Gamma-aminobutyric acid receptor subunit alpha-4 is a protein that in humans is encoded by the GABRA4 gene.
GABAA receptor-γ3, also known as GABRG3, is a protein which in humans is encoded by the GABRG3 gene.
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.
Gamma-aminobutyric acid receptor subunit gamma-1 is a protein that in humans is encoded by the GABRG1 gene. The protein encoded by this gene is a subunit of the GABAA receptor.
In pharmacology, GABAA receptor positive allosteric modulators, also known as GABAkines or GABAA receptor potentiators, are positive allosteric modulator (PAM) molecules that increase the activity of the GABAA receptor protein in the vertebrate central nervous system.
