PLASMA CLOZAPINE LEVELS AND THE TREATMENT OF L-DOPA-INDUCED PSYCHOSISIN PARKINSONS-DISEASE - A HIGH POTENCY EFFECT OF CLOZAPINE

The purpose of this study was to determine the plasma level of clozapi ne and its metabolite, N-desmethylclozapine, in Parkinson's disease pa tients with L-DOPA-induced psychosis responsive to clozapine. The psyc hotic symptoms of the three patients studied responded to low doses of clozapine with plasma levels of clozapine between 4.5 and 16.1 ng/ml and N-desmethylclozapine between 2.6 and 6.1 ng/ml, much below the pla sma clozapine levels usually found in clozapine-treated refractory sch izophrenia or affective disorders (range 100 to 687 ng/ml). Possible m echanisms that may account far clozapine's antipsychotic action in dop aminomimetic-induced psychosis in Parkinson's disease, including serot onin(2A) (5-HT2A) and dopamine D-4 receptor blockade, at plasma levels that would be ineffective in refractory schizophrenia, are discussed. It is suggested that 5-HT2A receptor blockade is the most likely basi s for the effectiveness of clozapine in L-DOPA psychosis.