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Updated: Jul 15, 2026

Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
Anaesthetic binding sites for etomidate and propofol on a GABAA receptor model
Valérie Campagna-Slater1, Donald F Weaver
1Department of Chemistry, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4J3.
Abstract:
Investigating the molecular basis of general anaesthetic activity at the GABA(A) ligand-gated ion channel is challenging due to the wide structural diversity among known general anaesthetics, and the lack of an experimental structure for the GABA(A) protein. In this molecular modelling study, two distinct binding cavities were identified within the beta(2) subunit of the transmembrane domain in a molecular model of the GABA(A) protein. The first, located near the centre of the alpha-helical bundle, contains Asn265 (TM2), which is essential for modulation by etomidate. The second, located near the TM1, TM3 and TM4 segments close to the membrane-extracellular interface, is capped by Met286 (TM3), a residue thought to be involved in the propofol binding site. Potential interactions of etomidate and propofol with other side-chains were also identified.
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