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11 30, 2022;12 (12):

Benzodiazepine Modulation of GABA Receptors: A Mechanistic Perspective.

Marcel P Goldschen-Ohm
Author Information
  1. Marcel P Goldschen-Ohm: Department of Neuroscience, University of Texas at Austin, Austin, TX 78712, USA. ORCID
PMID: 36551212 DOI: 10.3390/biom12121784

Abstract

Benzodiazepines (BZDs) are a class of widely prescribed psychotropic drugs that target GABA receptors (GABARs) 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(α1)(βX)(γ2) 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(α1)(βX)(γ2) 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.

Keywords

GABAA receptor benzodiazepines mechanism structure function

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Grants

  1. R01 GM148591/NIGMS NIH HHS

MeSH Term

Benzodiazepines
Receptors, GABA-A
gamma-Aminobutyric Acid

Chemicals

Benzodiazepines
Receptors, GABA-A
gamma-Aminobutyric Acid
Journal Article Review Research Support, Non-U.S. Gov't

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