Clozapine

Clozapine (HF 1854) is an antipsychotic used for the research of schizophrenia. Clozapine has high affinity for a number of neuroreceptors. Clozapine is a potent antagonist of dopamine D2 with a K_i of 75 nM. Clozapine inhibits the muscarinic M1 receptor and serotonin 5HT2A receptor with K_is of 9.5 nM and 4 nM, respectively^[1][2][3]. Clozapine is also a potent and selective agonist at the muscarinic M4 receptor (EC₅₀=11 nM)^[4]. IC50 & Target: Ki: 9.5 nM (M1), 51 nM (α2-adrenoceptor), 75 nM (D2)^[1]
EC50: 11 nM (M4)^[4] In Vitro: Clozapine (HF 1854) is a D2 receptor antagonist with a K_i of 75 nM, blocks the serotonin 5HT2A receptor with a K_i of 4 nM, inhibits the muscarinic M1 receptor with a K_i of 9.5 nM, blocks α2-adrenoceptor with a K_i value of 51 nM^[1].
Clozapine (0-1 μM; 24 h) downregulates 5-HT₆ and upregulates 5-HT₇ receptors in HeLa cells^[2].
Clozapine is a full agonist at the muscarinic M4 receptor (EC₅₀=11 nM) expressed in CHO cells^[4]. In Vivo: Clozapine (HF 1854) (25 mg/kg/day; i.p.; 21 days) shows antipsychotic effects in lysergic acid diethylamide-induced psychosis mouse model^[3].