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Neuropharmacologic Basis for Clozapine's Unique Profile

Rajiv Tandon, MD; John M. Kane, MD
Arch Gen Psychiatry. 1993;50(2):158-159. doi:10.1001/archpsyc.1993.01820140084012.
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To the Editor.—  In comparison with standard neuroleptics, clozapine is more effective in decreasing positive and negative symptoms in treatmentrefractory schizophrenic patients, and causes significantly fewer parkinsonian side effects and less tardive dyskinesia.1 In recent months, three distinct neurochemical hypotheses to explain clozapine's unique profile have been discussed in the Archives.2-4 Farde et al2 propose that clozapine's lower D2 dopamine receptor binding may explain the infrequent extrapyramidal syndromes (EPSs), and its higher D1 dopamine receptor binding may explain its superior efficacy. Meltzer and Stockmeier3 suggest that clozapine's significant serotonin (5-HT2) antagonist activity may explain both its unique properties. Pickar et al4 propose that clozapine's potent α2-noradrenergic antagonist activity (in addition to its anti-5-HT2 activity) may be relevant to its unique profile. Clozapine's greater affinity for the D4 dopamine receptor site5 has been implicated as well. Recent data


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