History of the Discovery and Clinical Introduction of Chlorpromazine

TLDR

Phenothiazines, first antipsychotic agents, originated from late 19th‑century German dye chemistry, were used as antiseptics and antimalarials until 1940, and chlorpromazine was synthesized in 1950 by Rhône‑Poulenc, with early North‑American publications in 1954 but delayed US adoption due to psychoanalytic traditions. This review analyzes the historical process of discovery and clinical introduction of chlorpromazine, one of the greatest advances of 20th‑century medicine. Chlorpromazine was first introduced in anaesthesiology and antishock protocols, then adopted for psychiatric use in 1952, with initial discrepancies between Parisian Val‑de‑Grâce and Sainte‑Anne hospital groups. By 1955 the antipsychotic efficacy of chlorpromazine was confirmed, consolidating neuroleptic therapy and sparking the psychopharmacological revolution in psychiatry.

Abstract

The historical process of discovery and clinical introduction of chlorpromazine, one of the greatest advances of 20th century medicine and history of psychiatry, is analyzed.In this review, we have studied the original works of pioneers in the discovery and clinical use of chlorpromazine, as well as the contributions of prestigious researchers (historians, pharmacologists, psychiatrists, etc.) about this topic.The discovery of phenothiazines, the first family of antipsychotic agents has its origin in the development of German dye industry, at the end of the 19th century (Graebe, Liebermann, Bernthsen). Up to 1940 they were employed as antiseptics, antihelminthics and antimalarials (Ehrlich, Schulemann, Gilman). Finally, in the context of research on antihistaminic substances in France after World War II (Bovet, Halpern, Ducrot) the chlorpromazine was synthesized at Rhône-Poulenc Laboratories (Charpentier, Courvoisier, Koetschet) in December 1950. Its introduction in anaesthesiology, in the antishock area (lytic cocktails) and "artificial hibernation" techniques, is reviewed (Laborit), and its further psychiatric clinical introduction in 1952, with initial discrepancies between the Parisian Val-de-Grâce (Laborit, Hamon, Paraire) and Sainte-Anne (Delay, Deniker) hospital groups. The first North-American publications on chlorpromazine took place in 1954 (Lehmann, Winkelman, Bower). The introduction of chlorpromazine in the USA (SKF) was more difficult due to their strong psychoanalytic tradition. The consolidation of the neuroleptic therapy took place in 1955, thanks to a series of scientific events, which confirmed the antipsychotic efficacy of the chlorpromazine.The discovery of the antipsychotic properties of chlorpromazine in the 1950s was a fundamental event for the practice of psychiatry and for the genesis of the so-called "psychopharmacological revolution."