Effects of clozapine metabolites and chronic clozapine treatment on rat brain GABAA receptors

European Journal of Pharmacology
G WongE R Korpi

Abstract

Similarly to clozapine, a clozapine metabolite, N-desmethylclozapine, but not clozapine N-oxide, antagonized brain gamma-aminobutyric acid type A (GABAA) receptors at high micromolar concentrations. However, daily subcutaneous injections of clozapine (10 and 25 mg/kg) and haloperidol (0.5 mg/kg) for 14 days failed to alter the modulation by GABA of rat cerebrocortical and cerebellar benzodiazepine ([3H]flunitrazepam) or convulsant (t-[35S]bicyclophosphorothionate) binding sites of the GABAA receptor. The results thus suggest that the GABAA receptor antagonism exerted by chronic in vivo clozapine treatment is weak as compared to this treatment's actions on certain monoamine receptors and is unlikely to be involved in the therapeutic actions of clozapine.

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Citations

Oct 6, 2007·Molecular Neurobiology·Gerhard Rammes, Rainer Rupprecht
Jul 20, 2002·Progress in Neurobiology·Esa R KorpiHartmut Lüddens
Nov 3, 2007·Progress in Neuro-psychopharmacology & Biological Psychiatry·Kelly J SkilbeckTina Hinton
Jul 1, 2017·The World Journal of Biological Psychiatry : the Official Journal of the World Federation of Societies of Biological Psychiatry·Irina PiatkovMark McLean
Sep 9, 2020·Progress in Neuro-psychopharmacology & Biological Psychiatry·Jun OmuraShigeru Morinobu

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