Clozapine N-oxide

A metabolite of clozapine and muscarinic DREADD agonist

Clozapine-N-oxide is a major metabolite of clozapine (Item No. 12059) and an activator of designer receptors exclusively activated by designer drugs (DREADDs) derived from human muscarinic acetylcholine receptors (EC50s = 16.7, 323, 17.4, 18.3, and 18.7 nM for PASMCs expressing hM1-5D receptors, respectively).1,2 It prevents action potential firing in cultured hippocampal neurons transiently expressing hM4D receptors.2 Clozapine-N-oxide increases glutamate in the nucleus accumbens core and inhibits cue-induced reinstatement of cocaine-seeking behavior in rats transfected with hM3Dq DREADD receptors.3

342.8

≥98%

1H-吲哚-3-醇，3-（硫酸氢），一钾盐 ≥98%

CNO

C[N]1(CCN(C2=NC(C=C(Cl)C=C3)=C3NC4=CC=CC=C24)CC1)=O

C18H19ClN4O

34233-69-7

≥ 4 years

: DMF: 2 mg/ml DMSO: 2 mg/ml PBS (pH 7.2): 1 mg/ml

1.Richelson, E., and Souder, T. Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sciences 68(1), 29-39 (2000).
2.Rummel-Kluge, C.,Komossa, K.,Schwarz, S., et al. Second-generation antipsychotic drugs and extrapyramidal side effects: A systematic review and meta-analysis of head-to-head comparisons. Schizophr.Bull. 38(1), 167-177 (2012).
3.Dain, J.G.,Nicoletti, J., and Ballard, F. Biotransformation of clozapine in humans. Drug Metabolism and Disposition 25(5), 603-609 (1997).
4.Eiermann, B.,Engel, G.,Johansson, I., et al. The involvement of CYP1A2 and CYP3A4 in the metabolism of clozapine. British Journal of Clinical Pharmacology 44(5), 439-446 (1997).
5.Zhang, W.V.,Ramzan, I., and Murray, M. Impaired microsomal oxidation of the atypical antipsychotic agent clozapine in hepatic steatosis. Journal of Pharmacology and Experimental Therapeutics 322(2), 770-777 (2007).
6.Ray, R.S.,Corcoran, A.E.,Brust, R.D., et al. Impaired respiratory and body temperature control upon acute serotonergic neuron inhibition. Science 333(6042), 637-642 (2012).
7.Kätzel, D.,Nocholson, E.,Schorge, S., et al. Chemical-genetic attenuation of focal neocortical seizures. Nat.Commun. 5, 1-9 (2014).

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