Plasma clozapine levels and the treatment of L-DOPA-induced psychosis in Parkinson's disease. A high potency effect of clozapine.
The purpose of this study was to determine the plasma level of clozapine and its metabolite, N-desmethylclozapine, in Parkinson's disease patients with L-DOPA-induced psychosis responsive to clozapine. The psychotic 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 plasma clozapine levels usually found in clozapine-treated refractory schizophrenia or affective disorders (range 100 to 687 ng/ml). Possible mechanisms that may account for clozapine's antipsychotic action in dopaminomimetic-induced psychosis in Parkinson's disease, including serotonin2A (5-HT2A) and dopamine D4 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 basis for the effectiveness of clozapine in L-DOPA psychosis.
Meltzer
H Y
HY
Department of Psychiatry, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Kennedy
J
J
Dai
J
J
Parsa
M
M
Riley
D
D
D000368:Aged; D003024:Clozapine / Q000031:analogs & derivatives / Q000097:blood* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007980:Levodopa / Q000009:adverse effects*; D008297:Male; D010300:Parkinson Disease / Q000150:complications* / Q000188:drug therapy; D011605:Psychoses, Substance-Induced / Q000150:complications* / Q000523:psychology
C058272:norclozapine; D007980:Levodopa; D003024:Clozapine