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September 1978

Thiethylperazine: Clinical Antipsychotic Efficacy and Correlation With Potency in Predictive Systems

Author Affiliations

From the Neuropsychopharmacology Research Unit, Department of Psychiatry, New York University School of Medicine, New York (Drs Rotrosen, Angrist, Gershon, and Ms Aronson); the Psychiatric Institute, New York (Drs Gruen and Sachar); Massachusetts General Hospital, Boston (Mr Denning); McLean Hospital, Belmont, Mass (Dr Matthysse); and the Department of Pharmacology, Mt Sinai School of Medicine, City University of New York (Drs Stanley and Wilk).

Arch Gen Psychiatry. 1978;35(9):1112-1118. doi:10.1001/archpsyc.1978.01770330086008

• A one-to-one relationship between clinical antipsychotic potency and pharmacologic dopaminergic antagonism is implicit in the dopamine hypothesis of neuroleptic action. Thiethylperazine maleate, a classical antiemetic phenothiazine, displays dopaminergic antagonism in behavioral, neurochemical, and neuroendocrine systems, but is paradoxical insofar as it is thought not to possess clinical neuroleptic activity. In three tests of dopaminergic antagonism-elevation of levels of CSF homovanillic acid in monkeys, striatal dihydroxyphenylacetic acid in rats, and prolactin in man-as well as in a clinical trial of neuroleptic efficacy in schizophrenics, thiethylperazine was fully active and approximately three times as potent as chlorpromazine. Differences in efficacy between this and earlier clinical studies can be accounted for on the basis of dosage.