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MedKoo Cat#: 527069 | Name: Clozapine N-oxide
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Clozapine N-oxide is a metabolite of clozapine, an atypical antipsychotic drug because it binds to serotonin as well as dopamine receptors. Clozapine is a partial agonist at the 5-HT1A subunit of the serotonin receptor, putatively improving depression, anxiety, and the negative cognitive symptoms associated with schizophrenia. A direct interaction of clozapine with the GABAB receptor has also been shown. GABAB receptor-deficient mice exhibit increased extracellular dopamine levels and altered locomotor behaviour equivalent to that in schizophrenia animal models.

Chemical Structure

Clozapine N-oxide
Clozapine N-oxide
CAS#34233-69-7 (N-oxide)

Theoretical Analysis

MedKoo Cat#: 527069

Name: Clozapine N-oxide

CAS#: 34233-69-7 (N-oxide)

Chemical Formula: C18H19ClN4O

Exact Mass: 342.1247

Molecular Weight: 342.83

Elemental Analysis: C, 63.06; H, 5.59; Cl, 10.34; N, 16.34; O, 4.67

Price and Availability

Size Price Availability Quantity
100mg USD 450.00 2 Weeks
250mg USD 750.00 2 Weeks
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Related CAS #
2250025-93-3 (2HCl) 54241-01-9 (HCl) 34233-69-7 (N-oxide) 5786-21-0 (free base)
Synonym
Clozapine N-oxide; CNO
IUPAC/Chemical Name
4-(8-chloro-5H-dibenzo[b,e][1,4]diazepin-11-yl)-1-methylpiperazine 1-oxide
InChi Key
OGUCZBIQSYYWEF-UHFFFAOYSA-N
InChi Code
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
SMILES Code
C[N+]1([O-])CCN(C2=NC3=CC(Cl)=CC=C3NC4=CC=CC=C42)CC1
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Product Data
Product Data
Instruction
View handling instruction
Biological target:
Clozapine N-oxide is a major metabolite of Clozapine and a human muscarinic designer receptors (DREADDs) agonist.
In vitro activity:
In vitro assessment demonstrated that CNO (clozapine N-oxide) is a substrate for P-glycoprotein (Pgp; efflux ratio, 20), thus providing a likely mechanism limiting CNO levels in the CNS.
In vivo activity:
5 mg/kg CNO (clozapine N-oxide) attenuated cocaine-induced locomotion in rats with a history of cocaine self-administration (Fig. 2). Reference: Neurosci Lett. 2018 May 1; 674: 132–135. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5899660/
Solvent mg/mL mM comments
Solubility
DMSO 44.2 128.99
DMF 2.0 5.83
Ethanol 8.0 23.34
PBS (pH 7.2) 1.0 2.92
Water 34.5 100.63
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 342.83 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.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Raper J, Morrison RD, Daniels JS, Howell L, Bachevalier J, Wichmann T, Galvan A. Metabolism and Distribution of Clozapine-N-oxide: Implications for Nonhuman Primate Chemogenetics. ACS Chem Neurosci. 2017 Jul 19;8(7):1570-1576. doi: 10.1021/acschemneuro.7b00079. Epub 2017 Mar 30. PMID: 28324647; PMCID: PMC5522181.
In vitro protocol:
1. Raper J, Morrison RD, Daniels JS, Howell L, Bachevalier J, Wichmann T, Galvan A. Metabolism and Distribution of Clozapine-N-oxide: Implications for Nonhuman Primate Chemogenetics. ACS Chem Neurosci. 2017 Jul 19;8(7):1570-1576. doi: 10.1021/acschemneuro.7b00079. Epub 2017 Mar 30. PMID: 28324647; PMCID: PMC5522181.
In vivo protocol:
1. Padovan-Hernandez Y, Knackstedt LA. Dose-dependent reduction in cocaine-induced locomotion by Clozapine-N-Oxide in rats with a history of cocaine self-administration. Neurosci Lett. 2018 May 1;674:132-135. doi: 10.1016/j.neulet.2018.03.045. Epub 2018 Mar 20. PMID: 29571824; PMCID: PMC5899660. 2. Manvich DF, Webster KA, Foster SL, Farrell MS, Ritchie JC, Porter JH, Weinshenker D. 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. doi: 10.1038/s41598-018-22116-z. PMID: 29497149; PMCID: PMC5832819.
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Mol Metab. 2017 Nov;6(11):1350-1359. doi: 10.1016/j.molmet.2017.08.009. Epub 2017 Sep 1. PubMed PMID: 29107283; PubMed Central PMCID: PMC5681239. 5: Li AJ, Wang Q, Ritter S. Selective pharmacogenetic activation of catecholamine subgroups in the ventrolateral medulla elicits key glucoregulatory responses. Endocrinology. 2017 Oct 24. doi: 10.1210/en.2017-00630. [Epub ahead of print] PubMed PMID: 29077837. 6: Campbell EJ, Mitchell CS, Adams CD, Yeoh JW, Hodgson DM, Graham BA, Dayas CV. Chemogenetic activation of the lateral hypothalamus reverses early life stress-induced deficits in motivational drive. Eur J Neurosci. 2017 Oct;46(7):2285-2296. doi: 10.1111/ejn.13674. Epub 2017 Sep 22. PubMed PMID: 28858406. 7: Gomez JL, Bonaventura J, Lesniak W, Mathews WB, Sysa-Shah P, Rodriguez LA, Ellis RJ, Richie CT, Harvey BK, Dannals RF, Pomper MG, Bonci A, Michaelides M. Chemogenetics revealed: DREADD occupancy and activation via converted clozapine. 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