Classics in Chemical Neuroscience: Chlorpromazine

ACS Chem Neurosci. 2019 Jan 16;10(1):79-88. doi: 10.1021/acschemneuro.8b00258. Epub 2018 Jul 16.

Abstract

The discovery of chlorpromazine in the early 1950s revolutionized the clinical treatment of schizophrenia, galvanized the development of psychopharmacology, and standardized protocols used for testing the clinical efficacy of antipsychotics. Furthermore, chlorpromazine expanded our understanding of the role of chemical messaging in neurotransmission and reduced the stigma associated with mental illness, facilitating deinstitutionalization in the 1960s and 1970s. In this review, we will discuss the synthesis, manufacturing, metabolism and pharmacokinetics, pharmacology, structure-activity relationship, and adverse effects of chlorpromazine. In conclusion, we summarize the history and significant contributions of chlorpromazine that have resulted in this potent first-generation antipsychotic maintaining its clinical relevance for nearly 70 years.

Keywords: Chlorpromazine; antipsychotic; dopamine; history; psychopharmacology; schizophrenia.

Publication types

  • Review

MeSH terms

  • Animals
  • Antipsychotic Agents / chemistry*
  • Antipsychotic Agents / therapeutic use*
  • Chlorpromazine / chemistry*
  • Chlorpromazine / therapeutic use*
  • Dopamine Antagonists / chemistry
  • Dopamine Antagonists / therapeutic use
  • Humans
  • Schizophrenia / drug therapy*
  • Schizophrenia / metabolism
  • Structure-Activity Relationship
  • Treatment Outcome

Substances

  • Antipsychotic Agents
  • Dopamine Antagonists
  • Chlorpromazine