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Clozapine N-oxide
- CNO
- Soluble in water and DMSO
- MF: C18H19ClN4O
- MW: 342.82
Description
Clozapine N-oxide (CNO) is a widely used chemogenetic ligand for engineered muscarinic DREADDs, including excitatory Gq-coupled and inhibitory Gi-coupled designer receptors. It enables reversible manipulation of defined cell populations expressing the corresponding engineered receptor.
CNO is also a metabolite of clozapine (Axon 1146). In rodents and other systems, CNO can undergo conversion back to clozapine, which may activate DREADDs and endogenous receptors at low concentrations; appropriate non-DREADD controls, pharmacokinetic considerations and dose minimization are therefore important.
Key Features
- Muscarinic DREADD agonist
- Enables reversible control of engineered Gq- and Gi-coupled receptors
- Clozapine metabolite
- Can be back-converted to clozapine in vivo
Applications
- DREADD chemogenetics
- Neuronal circuit manipulation
- Cell-type-specific signaling studies
- Behavioral neuroscience
- In vivo control experiments for chemogenetic ligands
More Information
| Parent CAS No. | 34233-69-7 |
|---|---|
| Chemical Name | 4-(8-Chloro-5H-dibenzo[b,e][1,4]diazepin-11-yl)-1-methylpiperazine 1-oxide |
| SMILES | N1C2C=CC=CC=2C(N2CC[N+]([O-])(C)CC2)=NC2C=C(Cl)C=CC1=2 |
| MFCD | MFCD00210190 |
| InChi | InChI=1S/C18H19ClN4O/c1-23(24)10-8-22(9-11-23)18-14-4-2-3-5-15(14)20-16-7-6-13(19)12-17(16)21-18/h2-7,12,20H,8-11H2,1H3 |
| InChiKey | OGUCZBIQSYYWEF-UHFFFAOYSA-N |
| CID | 135445691 |
| Short Description | DREADD agonist |
References
- V Nawaratne et al. New insights into the function of M4 muscarinic acetylcholine receptors gained using a novel allosteric modulator and a DREADD (designer receptor exclusively activated by a designer drug). Mol Pharmacol. 2008 Oct;74(4):1119-31.
- J Raper et al. Metabolism and Distribution of Clozapine-N-oxide: Implications for Nonhuman Primate Chemogenetics. ACS Chem Neurosci. 2017 Jul 19;8(7):1570-1576.
- DF Manvich 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.
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