University at Buffalo School of Pharmacy and Pharmaceutical Sciences Drug Information Response Documentation

Background: Clozapine is an atypical antipsychotic that differs from typical and other atypical antipsychotics as well. It differs from typical antipsychotics due to its low incidence of extrapyramidal symptoms and slight effect on dopamine sensitive prolactin. Another factor that makes it unique from most antipsychotic medications is its indication for treatment-refractory schizophrenia. This medication also has distinguishing features in its pharmacology due to its weak association with D2 receptors compared to the other atypicals. Clozapine primarily blocks D1 and D4 receptors. Furthermore, it has stronger anticholinergic properties versus other atypicals. However, despite its advantages, the use of clozapine can result in serious adverse effects such as orthostatic hypotension, sialorrhea, seizure, hepatotoxicity, and agranulocytosis. Because of the possibility of agranulocytosis, clozapine requires routine monitoring of WBC and ANC.