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ANALYSIS OF GABAA RECEPTOR FUNCTION AND DISSECTION OF THE PHARMACOLOGY OF BENZODIAZEPINES AND GENERA

ANALYSIS OF GABAA RECEPTOR FUNCTION AND DISSECTION OF THE PHARMACOLOGY OF BENZODIAZEPINES AND GENERA

  1. malsat
    From 2004.

    Abstract:
    GABAA receptors are molecular substrates for the regulation of vigi-
    lance, anxiety, muscle tension, epileptogenic activity, and memory functions, and the
    enhancement of GABAA receptor-mediated fast synaptic inhibition is the basis for
    the pharmacotherapy of various neurological and psychiatric disorders. Two kinds of
    GABAA receptor-targeted mutant mice have been generated: (a) knockout mice that
    lack individual GABAA receptor subunits (α1, α5, α6, β2, β3, γ 2, δ, and ρ1) and
    (b) knockin mice that carry point mutations affecting the action of modulatory drugs
    [α1(H101R), α2(H101R), α3(H126R), α5(H105R), and β3(N265M)]. Whereas the
    knockout mice have provided information primarily with respect to the regulation of
    subunit gene transcription, receptor assembly, and some physiological functions of in-
    dividual receptor subtypes, the point-mutated knockin mice in which specific GABAA
    receptor subtypes are insensitive to diazepam or some general anesthetics have re-
    vealed the specific contribution of individual receptor subtypes to the pharmacological
    spectrum of diazepam and general anesthetics.