Clozapine N-oxide is a pharmacologically inert metabolite of Clozapine, which is a potent 5-HT1C receptor antagonist. Clozapine N-oxide (CNO) is a DREADD (designer receptors exclusively activated by designer drug) agonist.
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•Biol Psychiatry. 2017 May 1;81(9):737-747.
Description
Clozapine N-oxide is a pharmacologically inert metabolite of Clozapine, which is a potent 5-HT1C receptor antagonist. Clozapine N-oxide (CNO) is a DREADD (designer receptors exclusively activated by designer drug) agonist.
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].
References
[1]. Wess J, et al. Novel designer receptors to probe GPCR signaling and physiology. Trends Pharmacol Sci. 2013 Jul;34(7):385-92.
[2]. Chang WH, et al. Reversible metabolism of clozapine and clozapine N-oxide in schizophrenic patients. Prog Neuropsychopharmacol Biol Psychiatry. 1998 Jul;22(5):723-39.
Preparing Stock Solutions
ConcentrationVolumeMass
1 mg
5 mg
10 mg
1 mM
2.9170 mL
14.5849 mL
29.1698 mL
5 mM
0.5834 mL
2.9170 mL
5.8340 mL
10 mM
0.2917 mL
1.4585 mL
2.9170 mL
Please refer to the solubility information to select the appropriate solvent.
References
[1]. Wess J, et al. Novel designer receptors to probe GPCR signaling and physiology. Trends Pharmacol Sci. 2013 Jul;34(7):385-92.
[2]. Chang WH, et al. Reversible metabolism of clozapine and clozapine N-oxide in schizophrenic patients. Prog Neuropsychopharmacol Biol Psychiatry. 1998 Jul;22(5):723-39.
Molecular Weight
342.82
Formula
C₁₈H₁₉ClN₄O
CAS No.
34233-69-7
Storage
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
6 months
-20°C
1 month
Shipping
Room temperature in continental US; may vary elsewhere
