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Chapter 25.Clozapine

Edited by:
https://doi.org/10.1176/appi.books.9781615371624.as25

Sections

History and Discovery | Structure–Activity Relations | Pharmacological Profile | Pharmacokinetics and Disposition | Pharmacogenetic Profile | Mechanism of Action | Indications and Efficacy | Side Effects and Toxicology | Drug–Drug Interactions | Conclusion

Excerpt

Clozapine has played a critical role in the history of therapeutics for psychosis. When clozapine was initially developed in the 1960s (following its synthesis in 1958 in Switzerland), there was skepticism as to whether an agent that barely caused catalepsy in rodents could be an effective antipsychotic. According to Hippius (1999), there was limited enthusiasm for this drug because its profile was inconsistent with the “neuroleptic dogma” that extrapyramidal side effects (EPS) were an essential feature of an antipsychotic agent. Nevertheless, Hippius and others challenged this dogma and supported clozapine’s development in Germany. As a result, clozapine was eventually marketed in a number of countries in Europe.

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