Clozapine

Clozapine is a dibenzodiazepine derivative with a highly complex mechanism of action and is classified as a multi-receptor antagonist. Its two principal actions are as follows. First, clozapine has relatively weak antagonism at dopamine receptors and shows unique receptor-binding kinetics, while also having some affinity for receptors such as D4. Through this, it reduces excessive dopaminergic activity in the central nervous system, decreases the hallucinations and delusions of schizophrenia, and is less likely than typical antipsychotics to cause extrapyramidal symptoms (EPS) or hyperprolactinemia. Second, it strongly antagonizes 5-HT2A and 5-HT2C receptors, helping reduce affective flattening, social withdrawal, and cognitive impairment, while also offsetting some adverse effects caused by dopamine blockade. In addition, it antagonizes M1 cholinergic receptors, which can cause dry mouth, constipation, and blurred vision; H1 histamine receptors, which can cause drowsiness and weight gain; and α1-adrenergic receptors, which can cause orthostatic hypotension.