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Affinity for Muscarinic Sites Predicts Extrapyramidal Effects

Solomon Snyder, MD; David Greenberg; Henry I. Yamamura, PhD

Arch Gen Psychiatry. 1974;31(1):58-61.

Abstract
With only a few exceptions, the phenothiazines and butyrophenones used in the treatment of schizophrenia appear to exert antischizophrenic actions to the same or closely similar degrees.

Both antischizophrenic and extrapyramidal effects apparently result from dopamine receptor blockade. Here, we report the influence of a variety of such antischizophrenic drugs on the brain's receptor for the muscarinic action of acetylcholine.

Extrapyramidal effects are inversely proportional to affinity for the muscarinic receptor. Thus, drugs such as clozapine and thioridazine hydrochloride apparently owe their low incidence of extrapyramidal effects to anticholinergic properties that compensate for their intrinsic extrapyramidal effects. Our findings provide a means to predict extrapyramidal actions of new potential antischizophrenic drugs.

Author Affiliations
Baltimore

From the departments of psychiatry and pharmacology, the Johns Hopkins University School of Medicine, Baltimore.

Footnotes
Accepted for publication Feb 28, 1974.

Reprint requests to the Johns Hopkins University School of Medicine, Department of Pharmacology and Experimental Therapeutics, 725 N Wolfe St, Baltimore, MD 21205 (Dr. Snyder).

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