| Indication | For use in patients with treatment-resistant schizophrenia. |
| Pharmacodynamics | Clozapine is a psychotropic agent belonging to the chemical class of benzisoxazole derivatives and is indicated for the treatment of schizophrenia. Clozapine is a selective monoaminergic antagonist with high affinity for the serotonin Type 2 (5HT2), dopamine Type 2 (D2), 1 and 2 adrenergic, and H1 histaminergic receptors. Clozapine acts as an antagonist at other receptors, but with lower potency. Antagonism at receptors other than dopamine and 5HT2 with similar receptor affinities may explain some of the other therapeutic and side effects of Clozapine. Clozapine's antagonism of muscarinic M1-5 receptors may explain its anticholinergic effects. Clozapine's antagonism of histamine H1 receptors may explain the somnolence observed with this drug. Clozapine's antagonism of adrenergic a1 receptors may explain the orthostatic hypotension observed with this drug. |
| Mechanism of action | Clozapine's antipsychotic action is likely mediated through a combination of antogistic effects at D2 receptors in the mesolimbic pathway and 5-HT2A receptors in the frontal cortex. D2 antagonism relieves positive symptoms while 5-HT2A antagonism alleviates negative symptoms. |
| Absorption | Rapid and almost complete |
| Volume of distribution | Not Available |
| Protein binding | 97% (bound to serum proteins) |
| Metabolism | Hepatic |
| Route of elimination | Approximately 50% of the administered dose is excreted in the urine and 30% in the feces. |
| Half life | 8 hours (range 4-12 hours) |
| Clearance | Not Available |
| Toxicity | Clozapine carries a black-box warning for agranulocytosis. |