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

Eur J Pharmacol. 1996 Oct 31;314(3):319-23. doi: 10.1016/s0014-2999(96)00671-1.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antipsychotic Agents / pharmacology*
  • Brain / drug effects*
  • Clozapine / analogs & derivatives
  • Clozapine / pharmacology*
  • Drug Evaluation, Preclinical
  • GABA Antagonists / pharmacology*
  • GABA-A Receptor Antagonists*
  • Haloperidol / pharmacology
  • In Vitro Techniques
  • Logistic Models
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors


  • Antipsychotic Agents
  • GABA Antagonists
  • GABA-A Receptor Antagonists
  • norclozapine
  • Clozapine
  • Haloperidol
  • clozapine N-oxide