Uses
Clozapine (HF 1854) dihydrochloride 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 Ki of 75 nM. Clozapine inhibits the muscarinic M1 receptor and serotonin 5HT2A receptor with Kis 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].
IC 50
5-HT
2A Receptor: 4 nM (Ki); 5-HT
6 Receptor; 5-HT
7 Receptor; mAChR1: 9.5 nM (Ki); mAChR4: 11 nM (EC
50); α2-adrenergic receptor: 51 nM (Ki); D
2 Receptor: 75 nM (Ki)
References
[1] Seeman P, et al. Clozapine, a fast-off-D2 antipsychotic. ACS Chem Neurosci. 2014 Jan 15;5(1):24-9. DOI:
10.1021/cn400189s[2] Zhukovskaya NL, et al. Clozapine downregulates 5-hydroxytryptamine6 (5-HT6) and upregulates 5-HT7 receptors in HeLa cells. Neurosci Lett. 2000 Jul 21;288(3):236-40. DOI:
10.1016/s0304-3940(00)01225-8[3] Moreno JL, et al. Persistent effects of chronic clozapine on the cellular and behavioral responses to LSD in mice. Psychopharmacology (Berl). 2013 Jan;225(1):217-26. DOI:
10.1007/s00213-012-2809-7[4] Zorn SH, et al. Clozapine is a potent and selective muscarinic M4 receptor agonist. Eur J Pharmacol. 1994 Nov 15;269(3):R1-2. DOI:
10.1016/0922-4106(94)90047-7[5] MILLAN M J. Improving the treatment of schizophrenia: focus on serotonin (5-HT)(1A) receptors.[J]. Journal of Pharmacology and Experimental Therapeutics, 2000, 295 3: 853-861.
[6] A SCHOTTE. Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding.[J]. Psychopharmacology, 1996, 124 1-2: 57-73. DOI:
10.1007/bf02245606[7] SHUNSKE TANAHASHI. Clozapine, but not haloperidol, enhances glial d-serine and L-glutamate release in rat frontal cortex and primary cultured astrocytes[J]. British Journal of Pharmacology, 2011, 165 5: 1543-1555. DOI:
10.1111/j.1476-5381.2011.01638.x[8] LYNNE E RUETER. Chronic low dose risperidone and clozapine alleviate positive but not negative symptoms in the rat neonatal ventral hippocampal lesion model of schizophrenia.[J]. Psychopharmacology, 2004, 176 3-4: 312-319. DOI:
10.1007/s00213-004-1897-4
