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Medical Pharmacology Chapter 16: Pharmacology of Antipsychotics Drugs
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Historical Context
The discovery of chlorpromazine in the early 1950s represents one of the most consequential events in the history of psychiatry.
Prior to this era, patients with schizophrenia and other psychotic disorders were largely managed with sedation, physical restraints, or invasive procedures such as insulin coma therapy and frontal lobotomy.
The introduction of the
first antipsychotic drug fundamentally altered that landscape.
In 1952, Jean Delay and Pierre Deniker,a psychiatrist and neurologist working at the Hôpital Sainte-Anne in Paris, systematically evaluated the antihistamine promethazine derivative RPh-4560 (later named chlorpromazine) in psychotic patients.
Their seminal report, presented at the Congrès des Médecins Aliénistes et Neurologistes de France in 1952,1 described dramatic reductions in agitation and psychotic symptoms without rendering patients unconscious, a property they distinguished as a novel "neuroleptic" effect, from the Greek meaning "to clasp the neuron."
Haloperidol, synthesized by Paul Janssen in 1958 and introduced clinically in the early 1960s, offered greater potency and became the prototypic high-potency FGA.
Together, chlorpromazine and haloperidol defined the clinical and pharmacological profile of the firstgeneration (or "typical" or "conventional") antipsychotics, a class that would dominate schizophrenia pharmacotherapy for the next three decades.
Mechanism of Action
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DISCLAIMER
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