Determination of clozapine in serum by radioreceptor assay versus high-performance liquid chromatography: possible detection of hydroxy-metabolites

Abstract

SUMMARYClozapine is an antipsychotic drug with few extrapyramidal motor side-effects, used to treat schizophrenia which is resistant to classical neuroleptic therapy. This report shows that norclozapine but not clozapine-N-oxide has the same D2 receptor affinity as clozapine. Assay results suggest a bimodal distribution which may be explained by CYF'IA2 polymorphism. Extensive metabolizers could produce other active metabolites, probably other hydroxy-clozapine derivatives.

Pharmacologically Active Metabolites of Currently Marketed Drugs: Potential Resources for New Drug Discovery and Development

“…69) Additionally, norclozapine was reported to possess the same dopamine D 2 receptor a‹nity as clozapine and even a higher a‹nity to the 5-HT receptor. 70,71) The plasma concentrations of norclozapine were correlated positively with granulocyte counts in schizophrenic patients. 72) Cyclosporine Cyclosporine is an immunosuppressive agent.…”