Clozapine hydrochloride

Product NameClozapine hydrochloride
CAS2711603-38-0
MFC18H20Cl2N4
MW363.28
EINECS
MOL FileMol File

Chemical Properties

solubility

DMF: 25 mg/ml
DMSO: 25 mg/ml
Ethanol: 25 mg/mlPBS (pH 7.2): 10 mg/ml

Usage And Synthesis

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].

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].

Animal Model:	Male 129 S6/Sv mice, lysergic acid diethylamide (LSD)-induced psychosis model^[3].
Dosage:	25 mg/kg/day.
Administration:	Intraperitoneal injection, 21 days.
Result:	Decreased head-twitch response, reduced 5-HT_2A mRNA, rescued induction of c-fos, but not egr-1 and egr-2.

IC 50

5-HT_2A Receptor: 4 nM (Ki); 5-HT₆ Receptor; 5-HT₇ Receptor; mAChR1: 9.5 nM (Ki); mAChR4: 11 nM (EC₅₀); α2-adrenergic receptor: 51 nM (Ki); D₂ 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

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