History and Discovery | Pharmacological Profile | Pharmacokinetics and Disposition | Mechanism of Action | Indications and Efficacy | Side Effects and Toxicology | Drug–Drug Interactions | Conclusion | References
A decade before clozapine was approved for marketing in the
United States, Janssen Pharmaceuticals established a program to
examine the potential role of serotonergic agents in schizophrenia.
Early interest in serotonergic agents stemmed from a preclinical
literature demonstrating that both behavioral effects of dopamine
agonists and haloperidol-induced catalepsy could be modulated by serotonin2 (5-HT2)
antagonists; in addition, the early butyrophenone derivative pipamperone,
which was observed to reduce agitation and improve social activity
in patients with severe depression, was found to possess primarily
5-HT2 antagonist activity (Ansoms et al. 1977; Leysen et al. 1978).