Benzodiazepine Modulation of GABA_A Receptors: A Mechanistic Perspective.

ABSTRACT: Benzodiazepines (BZDs) are a class of widely prescribed psychotropic drugs that target GABA_A receptors (GABA_ARs) to tune inhibitory synaptic signaling throughout the central nervous system. Despite knowing their molecular target for over 40 years, we still do not fully understand the mechanism of modulation at the level of the channel protein. Nonetheless, functional studies, together with recent cryo-EM structures of GABA_A(α1)₂(βX)₂(γ2)₁ receptors in complex with BZDs, provide a wealth of information to aid in addressing this gap in knowledge. Here, mechanistic interpretations of functional and structural evidence for the action of BZDs at GABA_A(α1)₂(βX)₂(γ2)₁ receptors are reviewed. The goal is not to describe each of the many studies that are relevant to this discussion nor to dissect in detail all the effects of individual mutations or perturbations but rather to highlight general mechanistic principles in the context of recent structural information.

SUBMITTER: Goldschen-Ohm MP 

PROVIDER: S-EPMC9775625 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature