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Submit ReviewClozapine N-oxide
Description: Activator of hM3Dq and hM4Di DREADDs
Alternative Names: CNO
Chemical Name: 8-Chloro-11-(4-methyl-4-oxido-1-piperazinyl)-5H-dibenzo[b,e][1,4]diazepine
Purity: ≥99% (HPLC)
Biological Activity for Clozapine N-oxide
Clozapine N-oxide is a synthetic ligand for human muscarinic engineered receptors, designer receptors activated by designer drugs (DREADD). Binds and activates hM3Dq and hM4Di DREADDs in vitro and in vivo. Metabolite of Clozapine (Cat. No. 0444). Shown to be a P-glycoprotein (P-gp) efflux pump substrate.
Example Applications of Clozapine N-oxide (CNO):
- Silences hippocampal neurons expressing hM4Di DREADDs in vitro
- Inhibits locomotor activity of mice expressing hM3Dq in GABAergic VTA neurons
- Inhibits short term memory retrieval in mice expressing hM4Di in hippocampal neurons
- Induces heat and mechanical hypersensitivity in mice expressing hM4Di in enkephalinergic neurons in the right lumbar dorsal horn
- Inhibits markers of social aggression in mice expressing hM4Di in hippocampal CA2 neurons
Alternative potent and selective hM3Dq and hM4Di DREADD agonists available: Deschloroclozapine and DREADD agonist 21
Water soluble salt also available.
This product contains 1 molar equivalent of ethanol.
Technical Data for Clozapine N-oxide
| M. Wt | 342.82 |
| Formula | C18H19ClN4O |
| Storage | Store at RT |
| Purity | ≥99% (HPLC) |
| CAS Number | 34233-69-7 |
| PubChem ID | 2819 |
| InChI Key | WYRDWWAASBTJLM-UHFFFAOYSA-N |
| Smiles | ClC(C=C3)=CC1=C3NC(C=CC=C2)=C2C(N4CC[N+](C)([O-])CC4)=N1 |
The technical data provided above is for guidance only. For batch specific data refer to the Certificate of Analysis.
Tocris products are intended for laboratory research use only, unless stated otherwise.
Solubility Data for Clozapine N-oxide
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 6.86 | 20 |
Preparing Stock Solutions for Clozapine N-oxide
The following data is based on the product molecular weight 342.82. Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 0.2 mM | 14.58 mL | 72.92 mL | 145.85 mL |
| 1 mM | 2.92 mL | 14.58 mL | 29.17 mL |
| 2 mM | 1.46 mL | 7.29 mL | 14.58 mL |
| 10 mM | 0.29 mL | 1.46 mL | 2.92 mL |
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Product Datasheets for Clozapine N-oxide
References for Clozapine N-oxide
References are publications that support the biological activity of the product.
Eiermann et al (1997) The involvement of CYP1A2 and CYP3A4 in the metabolism of cloz. Br.J.Clin.Pharmacol. 44 439 PMID: 9384460
Armbruster et al (2007) Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand. Proc.Natl.Acad.Sci.U.S.A. 104 5163 PMID: 17360345
Zaman et al (2014) LMO4 is essential for paraventricular hypothalamic neuronal activity and calcium channel expression to prevent hyperphagia. J.Neurosci. 34 140 PMID: 24381275
Gomez et al (2017) Chemogenetics revealed: DREADD occupancy and activation via converted cloz. Science 357 503 PMID: 28774929
Nakajima et al (2016) Gs-coupled GPCR signalling in AgRP neurons triggers sustained increase in food intake. Nat.Commun. 8 10268 PMID: 26743492
Roth (2016) DREADDs for Neuroscientists. Neuron 89 683 PMID: 26889809
If you know of a relevant reference for Clozapine N-oxide, please let us know.
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Keywords: Clozapine N-oxide, Clozapine N-oxide supplier, clozapine, metabolite, clozapine-N-oxide, DREADDs, DREADD, Ligands, muscarnic, receptors, designer, CNO, chemogenetics, Multidrug, Transporters, Non-selective, Muscarinics, 4936, Tocris Bioscience
139 Citations for Clozapine N-oxide
Citations are publications that use Tocris products. Selected citations for Clozapine N-oxide include:
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Gizowski & Bourque et al (2020) Sodium regulates clock time and output via an excitatory GABAergic pathway. Nature
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Amat (2017) Using c-kit to genetically target cerebellar molecular layer interneurons in adult mice. PLoS One 12 e0179347 PMID: 28658323
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Mark D et al (2017) Loss of Hyperdirect Pathway Cortico-Subthalamic Inputs Following Degeneration of Midbrain Dopamine Neurons. Neuron 95 1306-1318.e5 PMID: 28910619
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Simon M et al (2022) Hypothalamic AgRP neurons exert top-down control on systemic TNF-α release during endotoxemia. Curr Biol 32 4699-4706.e4 PMID: 36182699
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George Z et al (2022) Control of mammalian locomotion by ventral spinocerebellar tract neurons. Cell 185 328-344.e26 PMID: 35063074
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Jiang et al (2018) Cholinergic neurons in medial septum maintain anxiety-like behaviors induced by chronic inflammatory pain. Neurosci Letts 671 7 PMID: 29410218
Pina and Cunningham (2016) Ethanol-seeking behavior is expressed directly through an extended amygdala to midbrain neural circuit. Neurobiol Learn Mem 137 83 PMID: 27866960
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J Silvio et al (2019) Gβγ signaling to the chemotactic effector P-REX1 and mammalian cell migration is directly regulated by Gαq and Gα13 proteins. J Biol Chem 294 531-546 PMID: 30446620
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J Nicholas et al (2019) Natural and Drug Rewards Engage Distinct Pathways that Converge on Coordinated Hypothalamic and Reward Circuits. Neuron 103 891-908.e6 PMID: 31277924
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Giovanni et al (2020) Context-Specific Striatal Astrocyte Molecular Responses Are Phenotypically Exploitable. Neuron 108 1146-1162.e10 PMID: 33086039
Stewart A et al (2020) Modular, Circuit-Based Interventions Rescue Hippocampal-Dependent Social and Spatial Memory in a 22q11.2 Deletion Syndrome Mouse Model. Biol Psychiatry 88 710-718 PMID: 32682567
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Francois et al (2017) A Brainstem-Spinal Cord Inhibitory Circuit for Mechanical Pain Modulation by GABA and Enkephalins. Neuron 93 822 PMID: 28162807
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By
Anonymous on 06/15/2020
Assay Type: In Vivo
Species: Mouse
Cell Line/Tissue: neuron
1 mg/kg
Highly soluble and stable.
By
Anonymous on 01/04/2018
Assay Type: Ex Vivo
Species: Mouse
Soluble in 0.9% saline. Perfused in brain slice experiment with patch clamp study.
Literature in this Area
Tocris offers the following scientific literature in this area to showcase our products. We invite you to request* your copy today!
*Please note that Tocris will only send literature to established scientific business / institute addresses.
Chemogenetics Research Bulletin
Produced by Tocris, the chemogenetics research bulletin provides an introduction to chemogenetic methods to manipulate neuronal activity. It outlines the development of RASSLs, DREADDs and PSAMs, and the use of chemogenetic compounds. DREADD ligands and PSEMs available from Tocris are highlighted.
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G protein-coupled receptors (GPCRs) are intrinsically allosteric proteins. This poster provides insights into allosteric mechanisms of GPCR biology, highlighting key facets of GPCR allostery and therapeutic applications of allosteric modulators.
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GPCRs can interact with multiple distinct transducers or regulatory proteins and these can be preferentially engaged in an agonist-specific manner giving rise to biased agonism. This poster discusses cutting edge GPCR signaling pharmacology and highlights therapeutic applications of biased agonism.