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Seeman MV. History of the dopamine hypothesis of antipsychotic action. World J Psychiatry. 2021;11(7):355-364doi: 10.5498/wjp.v11.i7.355.
Seeman, M. V. (2021). History of the dopamine hypothesis of antipsychotic action. World journal of psychiatry, 11(7), 355-364. https://doi.org/10.5498/wjp.v11.i7.355
Seeman, Mary V. "History of the dopamine hypothesis of antipsychotic action." World journal of psychiatry vol. 11,7 (2021): 355-364. doi: https://doi.org/10.5498/wjp.v11.i7.355
Seeman MV. History of the dopamine hypothesis of antipsychotic action. World J Psychiatry. 2021 Jul 19;11(7):355-364. doi: 10.5498/wjp.v11.i7.355. eCollection 2021 Jul 19. PMID: 34327128; PMCID: PMC8311512.
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World J Psychiatry. 2021 Jul 19;11(7):355-364. doi: 10.5498/wjp.v11.i7.355. eCollection 2021 Jul 19.

History of the dopamine hypothesis of antipsychotic action.

World journal of psychiatry

Mary V Seeman

Affiliations

  1. Department of Psychiatry, University of Toronto, Toronto M5P 3L6, Ontario, Canada. [email protected].

PMID: 34327128 PMCID: PMC8311512 DOI: 10.5498/wjp.v11.i7.355

Abstract

The dopamine hypothesis of how antipsychotic drugs exert their beneficial effect in psychotic illness has an interesting history that dates back to 1950. This hypothesis is not to be confused with the dopamine hypothesis of schizophrenia; the aim of the latter is to explain the etiology of schizophrenia. The present review does not deal with schizophrenia but, rather, with the historical development of our current understanding of the dopamine-associated actions of the drugs that reduce the symptoms of psychosis. This historical review begins with the serendipitous discovery of chlorpromazine, a drug synthesized around a chemical core that initially served to produce man-made dyes. This molecular core subsequently contributed to the chemistry of antihistamines. It was with the aim of producing a superior antihistamine that chlorpromazine was synthesized; instead, it revolutionized the treatment of psychosis. The first hypothesis of how this drug worked was that it induced hypothermia, a cooling of the body that led to a tranquilization of the mind. The new, at the time, discoveries of the presence of chemical transmitters in the brain soon steered investigations away from a temperature-related hypothesis toward questioning how this drug, and other drugs with similar properties and effects, modulated endogenous neurotransmission. As a result, over the years, researchers from around the world have begun to progressively learn what antipsychotic drugs do in the brain.

©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.

Keywords: Binding assays; Chlorpromazine; G-Protein coupled receptors; Haloperidol; High affinity states; Receptor imaging

Conflict of interest statement

Conflict-of-interest statement: I am the widow of one of the investigators mentioned in the text.

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