PeptideDB

Clozapine N-oxide

CAS: 34233-69-7 F: C18H19ClN4O W: 342.82

Clozapine N-oxide is a major metabolite of Clozapine and a human muscarinic designer receptors (DREADDs) agonist. Clozap
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Bioactivity Clozapine N-oxide is a major metabolite of Clozapine and a human muscarinic designer receptors (DREADDs) agonist. Clozapine N-oxide activates the DREADD receptor hM3Dq and hM4Di. Clozapine N-oxide can cross the blood-brain barrier[1][2][3][4]. Clozapine is a potent dopamine antagonist and also a potent and selective muscarinic M4 receptor (EC50=11 nM) agonist[5][6].
Target Human muscarinic designer receptors (DREADDs)
Invitro Clozapine N-oxide (CNO) can bind to non-DREADD receptors at concentrations required for DREADD activation, and undergoes reverse-metabolism to its parent compound clozapine, an atypical antipsychotic that acts at a variety of pharmacological targets and produces numerous physiological and behavioral effects[2].
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. 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)[1].
Name Clozapine N-oxide
CAS 34233-69-7
Formula C18H19ClN4O
Molar Mass 342.82
Appearance Solid
Transport Room temperature in continental US; may vary elsewhere.
Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
Reference [1]. Wess J, et al. Novel designer receptors to probe GPCR signaling and physiology. Trends Pharmacol Sci. 2013 Jul;34(7):385-92. [2]. Manvich DF, et al. The DREADD agonist clozapine N-oxide (CNO) is reverse-metabolized to clozapine and produces clozapine-like interoceptive stimulus effects in rats and mice. Sci Rep. 2018 Mar 1;8(1):3840. [3]. van der Peet PL, et al. Gram scale preparation of clozapine N-oxide (CNO), a synthetic small molecule actuator for muscarinic acetylcholine DREADDs. MethodsX. 2018 Mar 23;5:257-267. [4]. Joseph Cichon, et al. Branch-specific dendritic Ca(2+) spikes cause persistent synaptic plasticity. Nature. 2015 Apr 9;520(7546):180-5. [5]. Silva RR, et al. Evaluation of Functional Selectivity of NSC 170973, Clozapine, and LASSBio-579, an Experimental Compound With Antipsychotic-Like Actions in Rodents, at G Protein and Arrestin Signaling Downstream of the Dopamine D2 Receptor. Front Pharmac [6]. Zorn SH, et al. Clozapine is a potent and selective muscarinic M4 receptor agonist. Eur J Pharmacol. 1994 Nov 15;269(3):R1-2.