8-​Chloro-​11-​(4-​methyl-​1-​piperazinyl)​-​5H-​dibenzo[b,e]​(1,4)​diazepine N-oxide

Cas No.:	34233-69-7
Chemical Name:	8-​Chloro-​11-​(4-​methyl-​1-​piperazinyl)​-​5H-​dibenzo[b,e]​(1,4)​diazepine N-oxide
SMILES:	[O-][N+]1(C)CCN(C2=C3NC4=CC(Cl)=CC=C4C=NC3=CC=C2)CC1
Formula:	C18H19ClN4O
M.Wt:	342.82
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:

Clozapine N-oxide (CNO) is a major metabolite of the anti-psychotic drug clozapine. Clozapine N-oxide is a agonist for the chemogenetic Designer Receptors Exclusively Activated by Designer Drug (DREADD) system.

In Vivo:

After a single intraperitoneal (i.p.) injection of Clozapine N-oxide (1 mg/kg) into mice, Clozapine N-oxide (CNO) plasma levels peak at 15 min and are very low after 2 h. Acutely administered CNO can be metabolically converted to Clozapine in other species such as human and guinea-pig. The metabolites that may form after chronic administration of CNO to DREADD-expressing mice (or other species) have not been studied systematically. However, even if back-transformation to Clozapine occurs after chronic CNO administration, it should be noted that Clozapine is a more potent (by ~10-fold) DREADD agonist than CNO itself. Moreover, confounding biological effects of potential CNO metabolites can be easily identified by including both saline- and CNO-treated WT animals in a particular DREADD study. Despite the short plasma half-life of CNO in mice, the biological effects that have been described after acute treatment of DREADD-expressing experimental animals are usually much longer (6-10 h). One possibility is that CNO tends to accumulate in tissues, although other scenarios are also feasible[1]. Using a general pharmacokinetic model for the interconversion process, the mean total clearances of Clozapine and Clozapine N-oxide (CNO) are 28.45 L/hr and 45.30 L/hr, respectively[2].