Structural pharmacology of GABAА receptors

Abstract

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the mammalian central nervous system (CNS), activating the inotropic type A receptors (GABAА receptors) to provide fast inhibition. GABAА receptors are the main target for various groups of drugs that are widely used in the treatment of CNS disorders. This review examines the relationship between the physiological effects of GABAА receptor activation and modulation by various substances (including medicinal compounds), the receptor's structure, and the interaction of these substances with specific modulatory sites. Recent advances in cryogenic electron microscopy have led to fundamental improvements in understanding the detailed organization and function of GABAА receptors. This review is based on both the latest structural data obtained from cryogenic electron microscopy and the results of biochemistry and electrophysiology studies, as well as molecular modelling.