Clozapine (HF 1854) dihydrochloride is utilized for researching psychiatric disorders. This compound exhibits high affinity for numerous neuroreceptors and acts as an effective antagonist of dopamine receptors, with a Ki value of 75 nM. Clozapine inhibits the muscarinic M1 receptor and serotonin 5HT2A receptor, with Ki values of 9.5 nM and 4 nM, respectively. Additionally, Clozapine is a selective agonist of the muscarinic M4 receptor (EC50 = 11 nM).

M4 mAChR:11 nM (EC50), α2-adrenoceptor:51 nM (Ki), D2 Receptor:75 nM (Ki), M1 mAChR:9.5 nM (Ki), 5-HT2A receptor:4 nM (Ki)

Clozapine (HF 1854) is a D2 receptor antagonist with a K\(_i\) of 75 nM, and it also blocks serotonin 5HT2A receptors with a K\(_i\) of 4 nM, inhibits muscarinic M1 receptors with a K\(_i\) of 9.5 nM, and blocks α2-adrenergic receptors with a K\(_i\) of 51 nM. At concentrations of 0-1 μM for 24 hours, Clozapine modulates receptor levels in HeLa cells by downregulating 5-HT 6 and upregulating 5-HT 7 receptors. It acts as a full agonist of muscarinic M4 receptors expressed in CHO cells, with an EC\(_{50}\) of 11 nM.

Clozapine (HF 1854) administered at 25 mg/kg/day via intraperitoneal injection for 21 days exhibits antipsychotic effects in a mouse model of psychosis induced by lysergic acid diethylamide.