The Chlorpromazine Enigma

• Published in: Journal of the history of the neurosciences Vol. 22; no. 1; pp. 14 - 29
• Main Author: Baumeister, Alan A.
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis Group 01.01.2013; Taylor & Francis Ltd
• Subjects: Antipsychotic Agents - history; Antipsychotic Agents - therapeutic use; Arvid Carlsson; Carlsson; Carlsson, Arvid; Chlorpromazine; Chlorpromazine - history; Chlorpromazine - therapeutic use; Drug therapy; History of medicine and histology; History, 20th Century; History, 21st Century; Humans; Nobel Prize; pharmacodynamics; Psychiatry - history; Psychotic Disorders - drug therapy; Psychotic Disorders - history; reserpine; Reserpine - history; Reserpine - therapeutic use; War of the Soups and Sparks
• ISSN: 0964-704X; 1744-5213
• DOI: 10.1080/0964704X.2012.664087

Two revolutionary drugs were introduced into psychiatry in the early 1950s for the treatment of agitated mental patients - reserpine and chlorpromazine. These drugs initiated the modern era of drug treatment for schizophrenia and other psychoses. Early research revealed that, although the pharmacological profiles of the two drugs overlapped considerably, they had different mechanisms of action. The mechanism of action of reserpine was determined first: it depletes monoamines from the brain and other tissues. By contrast, chlorpromazine has little or no effect on brain monoamine concentrations. The mystery created by two drugs that have similar pharmacological profiles but different mechanisms of action is the chlorpromazine enigma. For about eight years after the mechanism of action of reserpine was determined, researchers followed several false leads about the mechanism of action of chlorpromazine. Then, in 1963, Arvid Carlsson and Margit Lindqvist proposed that chlorpromazine (and haloperidol) work by blocking "monoaminergic" receptors. It was quickly determined that dopamine receptor blockade was the most important action. Although the idea of chemical communication between central neurons had yet to gain wide acceptance, this idea was central to resolving the chlorpromazine enigma.