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The mechanism of action of zopiclone

Published online by Cambridge University Press:  16 April 2020

A Doble ,
T Canton ,
C Malgouris ,
JM Stutzmann ,
O Piot ,
MC Bardone ,
C Pauchet  and
JC Blanchard
A Doble
Affiliation:
Biology Department, Rhône-Poulenc Korer SA, 13 quai Jules-Guesde, 94403Vitry-sur-Seine, France
T Canton
Affiliation:
Biology Department, Rhône-Poulenc Korer SA, 13 quai Jules-Guesde, 94403Vitry-sur-Seine, France
C Malgouris
Affiliation:
Biology Department, Rhône-Poulenc Korer SA, 13 quai Jules-Guesde, 94403Vitry-sur-Seine, France
JM Stutzmann
Affiliation:
Biology Department, Rhône-Poulenc Korer SA, 13 quai Jules-Guesde, 94403Vitry-sur-Seine, France
O Piot
Affiliation:
Biology Department, Rhône-Poulenc Korer SA, 13 quai Jules-Guesde, 94403Vitry-sur-Seine, France
MC Bardone
Affiliation:
Biology Department, Rhône-Poulenc Korer SA, 13 quai Jules-Guesde, 94403Vitry-sur-Seine, France
C Pauchet
Affiliation:
Biology Department, Rhône-Poulenc Korer SA, 13 quai Jules-Guesde, 94403Vitry-sur-Seine, France
JC Blanchard
Affiliation:
Biology Department, Rhône-Poulenc Korer SA, 13 quai Jules-Guesde, 94403Vitry-sur-Seine, France
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Summary

The mechanism of action of the cyclopyrrolone hypnotic drug zopiclone involves allosteric modulation of the GABAA receptor. Zopiclone displaces the binding of [3H]-flunitrazepam with an affinity of 28 nM, and enhances the binding of the channel blocker [35S]-TBPS. The binding of zopiclone, unlike that of hypnotic benzodiazepines, is not facilitated by GABA. Zopiclone does not distinguish between GABAA receptors containing different α-subunits (BZ1 and BZ2 phenotype). Studies with protein-modifying agents (eg diethylpyrocarbonate) and photoaffinity labelling suggest that cyclopyrrolones bind to a domain on the GABAA receptor different from the benzodiazepine binding domain. The consequence of this interaction with the GABAA receptor is to potentiate responses to GABA, as can be demonstrated by electrophysiological methods. Subchronic treatment of mice with high doses of zopiclone does not produce the changes in sensitivity of the GABAA receptor that are observed with hypnotic benzodiazepines.

Keywords

zopicloneGABAbenzodiazepinedependencephotoaffinity labelling
Type
Research Article
Information
European Psychiatry , Volume 10 , Issue S3: Satellite Symposium to the AEP Congress , 1995 , pp. 117s - 128s
Copyright
Copyright © Elsevier, Paris 1995

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