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 (6)
Reviews (1)
Literature (4)

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

6 Citations for Clozapine N-oxide dihydrochloride

Citations are publications that use Tocris products. Selected citations for Clozapine N-oxide dihydrochloride include:

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

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

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

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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