Clozapine (hydrochloride)

Clozapine is a partial agonist of the serotonin (5-HT) receptor subtype 5-HT1A (Ki = 180 nM). It also binds to the 5-HT2A, 5-HT2C, 5-HT3, 5-HT6, and 5-HT7 receptors (Kis = 3.3, 13, 110, 4, and 21 nM, respectively), as well as the histamine H1 and α1-adrenergic receptors (Kis = 2.1 and 23 nM, respectively). It does not bind to the 5-HT1B receptor and has a lower affinity for dopamine receptors (Kis = 540, 150, and 360 nM for D1-3, respectively). Clozapine induces the release of glutamate and D-serine, an agonist at the glycine site of the NMDA receptor, from astrocytes, and reduces the expression of astrocytic glutamate transporters. It reverses locomotor hyperactivity and deficits in prepulse inhibition of acoustic startle in a rat neonatal ventral hippocampal ibotenic lesion model of schizophrenia when administered at a dose of 2.5 mg/kg per day. Formulations containing clozapine have been used in the treatment of schizophrenia.