EFFECTS OF DESMETHYLCLOZAPINE ON FOS PROTEIN EXPRESSION IN THE FOREBRAIN - IN-VIVO BIOLOGICAL-ACTIVITY OF THE CLOZAPINE METABOLITE

Several products of the hepatic metabolism of clozapine are found in h igh concentrations in the plasma of schizophrenic patients treated wit h this atypical antipsychotic drug. One of these metabolites, N-desmet hylclozapine, has substantially different affinities for dopamine and serotonin metabolites than does the parent compound. However, it is no t known if this metabolite is active in vivo. We examined the effect o f acute administration of desmethylclozapine to rats on forebrain Fos protein expression. Clozapine induces expression of this immediate-ear ly gene in a distinct regional pattern in the brain. Desmethylclozapin e significantly increased Fos protein expression in the medial prefron tal cortex and nucleus accumbens, but not in the dorsolateral striatum , thus mirroring the effects of the parent compound. These data indica te that the desmethyl metabolite of clozapine has in vivo biological a ctivity. (C) 1998 American College of Neuropsychopharmacology. Publish ed by Elsevier Science Inc.