Clozapine

Clozapine is a partial agonist at the serotonin (5-HT) receptor subtype 5-HT1A (Ki = 180 nM).{22208,36950} 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 ?1-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.{22207} 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.{39941} Formulations containing clozapine have been used in the treatment of schizophrenia.