Plasma clozapine levels and the treatment of L-DOPA-induced psychosis in Parkinson's disease. A high potency effect of clozapine.

Abstract

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.

• Authors: H Y Meltzer, J Kennedy, J Dai, M Parsa, D Riley
• Journal: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology (Neuropsychopharmacology) Vol. 12 Issue 1 Pg. 39-45 (Feb 1995) ISSN: 0893-133X [Print] England
• PMID: 7766285 (Publication Type: Case Reports, Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• norclozapine
• Levodopa
• Clozapine

Topics

• Aged
• Clozapine (analogs & derivatives, blood, therapeutic use)
• Female
• Humans
• Levodopa (adverse effects)
• Male
• Parkinson Disease (complications, drug therapy)
• Psychoses, Substance-Induced (complications, psychology)