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Updated: May 31, 2026

Methods for Studying the Mechanisms of Action of Antipsychotic Drugs in Caenorhabditis elegans
Published on: February 4, 2014
Evidence that clozapine directly interacts on the GABAB receptor
Ying Wu1, Monica Blichowski, Zafiris J Daskalakis
1Program in Neuroscience and Mental Health, University of Toronto fCentre for Addiction and Mental Health, Toronto, Ontario, Canada.
Abstract:
Neurophysiological studies suggest that clozapine may facilitate γ-aminobutyric acid (GABAergic) neurotransmission. Therefore, we studied the interaction between clozapine and the GABAB receptor (GABABR). We showed that clozapine, and not N-desmethylclozapine, which is a metabolite of clozapine, increased the binding of the GABABR antagonist, [³H]-CGP54626A, at GABABRs. Linear regression analysis showed that the correlation between the dose of clozapine and the increase of [³H]-CGP54626A binding was significant. The curve of specific [³H]-CGP54626A binding in competition with different concentrations of GABA was left shifted in the presence of clozapine. With HEK293 cells overexpressing GABABR, we showed that clozapine had a significant increase of [³H]-CGP54626A binding at GABABR1 subunit, which provided a clue of the potential therapeutic target of clozapine.
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