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Submit ReviewClozapine N-oxide dihydrochloride
Description: Activator of hM3Dq and hM4Di DREADDs; water soluble version of Clozapine N-oxide (Cat. No. 4936)
Alternative Names: CNO (water-soluble)
Chemical Name: 8-Chloro-11-(4-methyl-4-oxido-1-piperazinyl)-5H-dibenzo[b,e][1,4]diazepine dihydrochloride
Purity: ≥99% (HPLC)
Biological Activity for Clozapine N-oxide dihydrochloride
Clozapine N-oxide dihydrochloride is a water-soluble salt of Clozapine N-oxide (Cat. No.4936). Activator of muscarinic DREADDs. Clozapine N-oxide dihydrochloride exhibits improved bioavailability (6 - 7-fold higher plasma concentration) compared with CNO, with less conversion to clozapine in animal studies.
Compound Libraries for Clozapine N-oxide dihydrochloride
Clozapine N-oxide dihydrochloride is also offered as part of the Tocriscreen 2.0 Max. Find out more about compound libraries available from Tocris.
Technical Data for Clozapine N-oxide dihydrochloride
| M. Wt | 415.74 |
| Formula | C18H19ClN4O.2HCl |
| Storage | Desiccate at RT |
| Purity | ≥99% (HPLC) |
| CAS Number | 2250025-93-3 |
| PubChem ID | 137187247 |
| InChI Key | MBRGKRXDVKTUPT-UHFFFAOYSA-N |
| Smiles | ClC(C=C1)=CC2=C1NC(C=CC=C3)=C3C(N4CC[N+](C)([O-])CC4)=N2.Cl.Cl |
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 dihydrochloride
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| water | 41.57 | 100 | |
| DMSO | 41.57 | 100 |
Preparing Stock Solutions for Clozapine N-oxide dihydrochloride
The following data is based on the product molecular weight 415.74. 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 |
|---|---|---|---|
| 1 mM | 2.41 mL | 12.03 mL | 24.05 mL |
| 5 mM | 0.48 mL | 2.41 mL | 4.81 mL |
| 10 mM | 0.24 mL | 1.2 mL | 2.41 mL |
| 50 mM | 0.05 mL | 0.24 mL | 0.48 mL |
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Product Datasheets for Clozapine N-oxide dihydrochloride
References for Clozapine N-oxide dihydrochloride
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
Ambruster 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
Roth et al (2016) DREADDs for Neuroscientists. Neuron 89 683 PMID: 26889809
Nakajima et al (2016) Gs-coupled GPCR signalling in AgRP neurons triggers sustained increase in food intake. Nat.Commun. 8 10268 PMID: 26743492
Allen et al (2019) A comparative study of the pharmacokinetics of cloz. N-oxide and cloz. N-oxide hydrochloride salt in rhesus macaques. J.Pharmacol.Exp.Ther. 368 199 PMID: 30523062
If you know of a relevant reference for Clozapine N-oxide dihydrochloride, please let us know.
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Keywords: Clozapine N-oxide dihydrochloride, Clozapine N-oxide dihydrochloride supplier, Clozapine, N-oxide, 2HCl, metabolite, DREADDs, Ligands, muscarnic, designer, receptors, CNO, water, soluble, chemogenetics, (water-soluble), Multidrug, Transporters, Non-selective, Muscarinics, 6329, Tocris Bioscience
21 Citations for Clozapine N-oxide dihydrochloride
Citations are publications that use Tocris products. Selected citations for Clozapine N-oxide dihydrochloride include:
Henry A et al (2020) Directed Evolution of a Selective and Sensitive Serotonin Sensor via Machine Learning. Cell 183 1986-2002.e26 PMID: 33333022
Jonathan D et al (2020) Glutamatergic projections from homeostatic to hedonic brain nuclei regulate intake of highly palatable food. Sci Rep 10 22093 PMID: 33328492
Laura E et al (2023) Effects of clozapine-N-oxide and compound 21 on sleep in laboratory mice. Elife 12 PMID: 36892930
David M et al (2023) Gestational ethanol exposure impairs motor skills in female mice through dysregulated striatal dopamine and acetylcholine function. Neuropsychopharmacology PMID: 37188849
Khodai et al (2018) PACAP Neurons in the Ventromedial Hypothalamic Nucleus Are Glucose Inhibited and Their Selective Activation Induces Hyperglycaemia. Front Endocrinol (Lausanne) 9 632 PMID: 30425681
Fernandez et al (2018) Thalamic reticular control of local sleep in mouse sensory cortex. Elife 7 PMID: 30583750
Benjamin R et al (2021) Somatostatin interneurons activated by 5-HT2A receptor suppress slow oscillations in medial entorhinal cortex. Elife 10 PMID: 33789079
Wei et al (2021) Neural circuits and activity dynamics underlying sex-specific effects of chronic social isolation stress. Cell Rep 34 108874 PMID: 33761364
Stephen D et al (2021) Area Postrema Cell Types that Mediate Nausea-Associated Behaviors. Neuron 109 461-472.e5 PMID: 33278342
Jean-Pierre et al (2021) Inhibitory control of synaptic signals preceding locomotion in mouse frontal cortex. Cell Rep 37 110035 PMID: 34818555
Hye-Jin et al (2021) Repeated exposure with short-term behavioral stress resolves pre-existing stress-induced depressive-like behavior in mice. Nat Commun 12 6682 PMID: 34795225
Andrea et al (2022) Prefrontal feature representations drive memory recall. Nature 608 153-160 PMID: 35831504
Yuval et al (2022) Astrocytes play a critical role in mediating the effect of acute ethanol on central amygdala glutamatergic transmission. Neuropharmacology 205 108918 PMID: 34896402
Frank et al (2022) A brainstem circuit for nausea suppression. Cell Rep 39 110953 PMID: 35705049
Gilberto et al (2022) A hypothalamic dopamine locus for psychostimulant-induced hyperlocomotion in mice. Nat Commun 13 5944 PMID: 36209152
Qiang et al (2022) Female sexual behavior is disrupted in a preclinical mouse model of PCOS via an attenuated hypothalamic nitric oxide pathway. Proc Natl Acad Sci U S A 119 e2203503119 PMID: 35867816
Domokos et al (2022) Microglia modulate blood flow, neurovascular coupling, and hypoperfusion via purinergic actions. J Exp Med 219 PMID: 35201268
Chang et al (2019) The Ventral Hippocampus Controls Stress-Provoked Impulsive Aggression through the Ventromedial Hypothalamus in Post-Weaning Social Isolation Mice. Cell Rep 28 1195 PMID: 31365864
Torre-Muruzabal et al (2019) Chronic nigral neuromodulation aggravates behavioral deficits and synaptic changes in an a-synuclein based rat model for Parkinson's disease. Acta Neuropathol Commun 7 160 PMID: 31640762
Boender et al (2020) Striatal Astrocytes Shape Behavioral Flexibility via Regulation of the Glutamate Transporter EAAT2. Biol Psychiatry 89 1045 PMID: 33516457
Sheahan et al (2020) The neurokinin-1 receptor is expressed with gastrin-releasing peptide receptor in spinal interneurons and modulates itch. J Neurosci 40 8816 PMID: 33051347
Do you know of a great paper that uses Clozapine N-oxide dihydrochloride from Tocris? Please let us know.
Reviews for Clozapine N-oxide dihydrochloride
Average Rating: 5 (Based on 1 Review.)
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Great H2O soluble version of CNO.
By
Melanie Pina on 05/23/2019
Assay Type: In Vivo
Species: Mouse
Great water soluble version that worked beautifully in my hands. Used to stimulate virally-expressed hM4Di for behavioral neuroscience applications. CNO-induced activation of hM4Di significantly inhibited neuronal activation as confirmed via c-Fos staining.
Literature in this Area
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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.