On the GABAA receptor: a molecular modeling approach.

Article date: 1989/6/1

PubMed ID: 2547082

Journal name: Journal of neuroscience research (ISSN: 0360-4012)


Bicuculline methobromide, a complex alkaloid, antagonizes in some unknown manner the action of GABA, an important inhibitory transmitter in the CNS. To help understand the mechanism of this antagonism we have employed molecular modeling techniques to assess the similarity and difference between this antagonist and GABA plus four direct GABA agonists. Topological and electronic charge congruence between these five molecules was examined in great detail. It was found that each of the five molecules has three clearly defined atoms that serve as attachment points at the GABAA receptor site. It is hypothesized that an additional negatively charged atom on bicuculline serves as an additional point of attachment that blocks the nearby chloride ion channel. The model presented offers an explanation of why muscimol acts as a better agonist than GABA as well as rationalizing why (+)-bicuculline acts as an antagonist but (-)-bicuculline does not.

This document is available from: http://directlinks.cc/files/muscimol/2547082.pdf

Author List: Aprison M H, Lipkowitz K B

Publication Types: Journal Article; Research Support, U.S. Gov't, P.H.S.

Substances mentioned in the article: Receptors, GABA-A; gamma-Aminobutyric Acid; Bicuculline;

Mesh terms: Bicuculline/metabolism; Binding Sites; Models, Molecular; Receptors, GABA-A/analysis; gamma-Aminobutyric Acid/analogs & derivatives;

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