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