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The ionotropic GABA A receptor protein complex is also the molecular target of the benzodiazepine class of tranquilizer drugs. Benzodiazepines do not bind to the same receptor site on the protein complex as does the endogenous ligand GABA (whose binding site is located between α- and β-subunits), but bind to distinct benzodiazepine binding sites situated at the interface between the α- and ...
GABA receptor antagonists are drugs that inhibit the action of GABA. In general these drugs produce stimulant and convulsant effects, and are mainly used for counteracting overdoses of sedative drugs. Examples include bicuculline, securinine and metrazol, and the benzodiazepine GABA A receptor antagonist flumazenil.
Flumazenil (also known as flumazepil, code name Ro 15-1788 [3]) is a selective GABA A receptor antagonist [4] administered via injection, otic insertion, or intranasally. Therapeutically, it acts as both an antagonist and antidote to benzodiazepines (particularly in cases of overdose), through competitive inhibition .
A subclass of ionotropic GABA receptors, insensitive to typical allosteric modulators of GABA A receptor channels such as benzodiazepines and barbiturates, [27] [28] [29] was designated GABA ะก receptor. [30] [31] Native responses of the GABA C receptor type occur in retinal bipolar or horizontal cells across vertebrate species. [32] [33] [34] [35]
The subset of GABA A receptors that also bind benzodiazepines are referred to as benzodiazepine receptors (BzR). The GABA A receptor is a heteromer composed of five subunits, the most common ones being two αs, two βs, and one γ (α 2 β 2 γ1). For each subunit, many subtypes exist (α 1–6, β 1–3, and γ 1–3).
Fig 2. Schematic diagram of a GABAA receptor protein ((α1)2(β2)2(γ2)) which illustrates the five combined subunits that form the protein, the chloride (Cl-) ion channel pore, the two GABA active binding sites at the α1 and β2 interfaces, and the benzodiazepine (BZD) allosteric binding site at the α1 and γ2 interface.
Iomazenil (also known as Ro16-0154, INN, USAN; benzodine) is an antagonist and partial inverse agonist of benzodiazepine and a potential treatment for alcohol use disorder. The compound was introduced in 1989 by pharmaceutical company Hoffmann-La Roche as an Iodine-123 -labelled SPECT tracer for imaging benzodiazepine receptors ( GABA A ...
A GABA A receptor negative allosteric modulator is a negative allosteric modulator (NAM), or inhibitor, of the GABA A receptor, a ligand-gated ion channel of the major inhibitory neurotransmitter γ-aminobutyric acid (GABA). [1] [2] They are closely related and similar to GABA A receptor antagonists.
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