Clozapine N-oxide
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't 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].
Product Specifications
CAS Number
[34233-69-7]
UNSPSC
12352005
Hazard Statement
H301, H336
Target
Dopamine Receptor; Drug Metabolite; mAChR
Type
Reference compound
Related Pathways
GPCR/G Protein; Metabolic Enzyme/Protease; Neuronal Signaling
Applications
Neuroscience-Neuromodulation
Field of Research
Neurological Disease
Assay Protocol
https://www.medchemexpress.com/Clozapine-N-oxide.html
Purity
99.98
Solubility
DMSO : 100 mg/mL (ultrasonic) |H2O : < 0.1 mg/mL (ultrasonic)
Smiles
[O-][N+]1(C)CCN(C2=NC3=CC(Cl)=CC=C3NC4=CC=CC=C42)CC1
Molecular Formula
C18H19ClN4O
Molecular Weight
342.82
Precautions
H301, H336
References & Citations
[1]Wess J, et al. Novel designer receptors to probe GPCR signaling and physiology. Trends Pharmacol Sci. 2013 Jul;34 (7) :385-92.|[2]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 Pharmacol. 2019 Jun 4;10:628.|[3]Zorn SH, et al. Clozapine is a potent and selective muscarinic M4 receptor agonist. Eur J Pharmacol. 1994 Nov 15;269 (3) :R1-2.|[4]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.|[5]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.|[6]Joseph Cichon, et al. Branch-specific dendritic Ca (2+) spikes cause persistent synaptic plasticity. Nature. 2015 Apr 9;520 (7546) :180-5.|[7]Rodd ZA, et al. CNO Administration Increases Dopamine and Glutamate in the Medial Prefrontal Cortex of Wistar Rats: Further Concerns for the Validity of the CNO-activated DREADD Procedure. Neuroscience. 2022 May 21;491:176-184.
Shipping Conditions
Room Temperature
Storage Conditions
-20°C, 3 years; 4°C, 2 years (Powder)
Scientific Category
Reference compound1
Clinical Information
No Development Reported
Isoform
MAChR3; mAChR4
Citation 01
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