Clozapine N-oxide dihydrochloride

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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)
Citations (21)
Reviews (1)
Literature (3)

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
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
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.

Select a batch to recalculate based on the batch molecular weight:
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

Certificate of Analysis / Product Datasheet
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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.

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:

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

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

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

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

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

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

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

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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.

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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!

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