Name: Clozapine N-oxide (CNO)
Brand: GlpBio
SKU: GC10822
Availability: InStock
Rating: 5 (30 reviews)

Product has been cited by 5 publications

Related Biological Data

Specific manipulations with the VTA DA neuron activity alter depression-like behaviors The immobility time of the AAV-DIO-hM4D-mCherryinjected (C) and the AAV-DIO-mCherry-injected (D) mice in the TST (i) or the FST (ii) were measured before and 15 min after the administration of CNO.
One week after the injection of AAV-DIO-hM4D(Gi)-mCherry/AAV-DIO-hM3D-mCherry or AAV-DIO-mCherry and before the behavioral tests, clozapine N-oxide, CNO (3.3 mg kg-1, i.p.)(GLPBIO) was scheduled 15 minutes prior to the test.
Cell reports 37.5 (2021): 109936. PMID: 34731609 IF: 9.424
Related Biological Data

Chemogenetic activation of MCH neurons induced anxiety-like behaviors in mice.(C) Effects of 0.3 mg/kg and 0.15 mg/kg CNO on OFT, EPM and MBT in wild type mice. (n = 6–8 mice per group).
On the experiment day, CNO (0.15 mg/kg)(GLPBIO) was injected intraperitoneally to induce the activation of hM3Dqpositive MCH neurons in the LHA 20 min prior to the anxiety behaviors tests.
Frontiers in Pharmacology 13 (2022): 906057. PMID: 36016574 IF: 5.6

Product Documents

Quality Control & SDS

View current batch:

Purity: >98.00%

Protocol

Cell experiment [1]:
Cell lines	Primary rat cortical cells
Preparation Method	Receptor parameters (density affinity and mRNA levels) and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNA levels in rat primary cortical cells after 24 h of Clozapine N-oxide(CNO) (200/400 ng/ml) treatment under in vitro conditions
Reaction Conditions	Clozapine N-oxide(CNO) (200/400 ng/ml)for 24h
Applications	A significant decrease was found in primary cortical cells for 5-HT(2) receptor density (Clozapine N-oxide(CNO) 200/ 400/ 200 and Cloz-N-oxide 200 vs. control) and 5-HT(2A) receptor mRNA levels (Clozapine N-oxide(CNO) 200 vs. control).
Animal experiment [2]:
Animal models	β-RQ and β-RS Tg mice
Preparation Method	To determine the in vivo effects of acute activation of β-cell G q /11 or G S signaling on glucose homeostasis, mice were injected with increased doses of Clozapine N-oxide(CNO) (0.0001-10 mg/kg) and blood glucose levels were monitored for 2 h. Before the experiment began, all mice were free to eat and were given.
Dosage form	0.0001-10 mg/kg Clozapine N-oxide(CNO) for 2 h
Applications	In both β-R-q and β-R-s Tg mice, Clozapine N-oxide(CNO) treatment resulted in a dose-dependent decrease in blood glucose levels and increased plasma insulin concentrations, demonstrating that the degree of β cell G protein signaling could be titrated according to the Clozapine N-oxide(CNO) dose administered.
References: [1]: Heiser P, Schulte E, et,al. Effects of clozapine and its metabolites on the 5-HT2 receptor system in cortical and hippocampal cells in vitro. Prog Neuropsychopharmacol Biol Psychiatry. 2004 Mar;28(2):297-302. doi: 10.1016/j.pnpbp.2003.10.008. PMID: 14751426. [2]: Guettier JM, Gautam D, et,al. A chemical-genetic approach to study G protein regulation of beta cell function in vivo. Proc Natl Acad Sci U S A. 2009 Nov 10;106(45):19197-202. doi: 10.1073/pnas.0906593106. Epub 2009 Oct 26. PMID: 19858481; PMCID: PMC2767362.

Clozapine N-oxide(CNO) is a potent dopamine antagonist and also a potent and selective muscarinic M4 receptor (EC₅₀=11 nM) agonist^[5，6].Clozapine N-oxide also is a major metabolite of Clozapine and a human muscarinic designer receptors (DREADDs) agonist^[1,2]. Clozapine N-oxide activates the DREADD receptor hM3Dq and hM4Di. Clozapine N-oxide(CNO) is a pharmacologically inert molecule that lacks a significant (<1 μm) affinity for the receptor^[3]. Clozapine N-oxide(CNO) is highly bioavailable in rodents and humans^[4]

Clozapine N-oxide(CNO) significantly reduces the density of the 5-HT2 receptor in rat cortical cells, A significant decrease was found in primary cortical cells for 5-HT(2) receptor density and 5-HT(2A) receptor mRNA levels^[7].

In both β-R-q and β-R-s Tg mice, Clozapine N-oxide(CNO) treatment resulted in a dose-dependent decrease in blood glucose levels and increased plasma insulin concentrations, demonstrating that the degree of β cell G protein signaling could be titrated according to the Clozapine N-oxide(CNO) dose administered^[8].Oral Clozapine N-oxide(CNO) administration via drinking water to mice expressing rM3Dq in pancreatic β-cells led to robust metabolic phenotypes, indicating that significant amounts of Clozapine N-oxide(CNO) are absorbed from the gastrointestinal tract^[9].It created transgenic mice expressing an evolved G protein-coupled receptor (hM3Dq) selectively activated by the pharmacologically inert, orally bioavailable drug Clozapine N-oxide (CNO).Local field potential and single-neuron recordings revealed that peripheral administration of Clozapine N-oxide(CNO) activated hippocampal neurons selectively in hM3Dq-expressing mice. Behavioral correlates of neuronal activation included increased locomotion, stereotypy, and limbic seizures^[10].

References:
[1]: Wess J, Nakajima K, et,al. Novel designer receptors to probe GPCR signaling and physiology. Trends Pharmacol Sci. 2013 Jul;34(7):385-92. doi: 10.1016/j.tips.2013.04.006. Epub 2013 Jun 13. PMID: 23769625; PMCID: PMC3758874.
[2]: Manvich DF, Webster KA, et,al. 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.
[3]: Weiner DM, Meltzer HY, et,al. The role of M1 muscarinic receptor agonism of N-desmethylclozapine in the unique clinical effects of clozapine. Psychopharmacology (Berl). 2004 Dec;177(1-2):207-16. doi: 10.1007/s00213-004-1940-5. Epub 2004 Jul 16. PMID: 15258717.
[4]: Bender D, Holschbach M, et,al. Synthesis of n.c.a. carbon-11 labelled clozapine and its major metabolite clozapine-N-oxide and comparison of their biodistribution in mice. Nucl Med Biol. 1994 Oct;21(7):921-5. doi: 10.1016/0969-8051(94)90080-9. PMID: 9234345.
[5]: Silva RR, Parreiras-E-Silva LT, et,al. Evaluation of Functional Selectivity of Haloperidol, Clozapine, and LASSBio-579, an Experimental Compound With Antipsychotic-Like Actions in Rodents, at G Protein and Arrestin Signaling Downstream of the Dopamine D2 Receptor. Front Pharmacol. 2019 Jun 4;10:628. doi: 10.3389/fphar.2019.00628. PMID: 31214037; PMCID: PMC6558205.
[6]: Zorn SH, Jones SB, et,al. Clozapine is a potent and selective muscarinic M4 receptor agonist. Eur J Pharmacol. 1994 Nov 15;269(3):R1-2. doi: 10.1016/0922-4106(94)90047-7. PMID: 7895765.
[7]: Heiser P, Schulte E, et,al. Effects of clozapine and its metabolites on the 5-HT2 receptor system in cortical and hippocampal cells in vitro. Prog Neuropsychopharmacol Biol Psychiatry. 2004 Mar;28(2):297-302. doi: 10.1016/j.pnpbp.2003.10.008. PMID: 14751426.
[8]: Guettier JM, Gautam D, et,al. A chemical-genetic approach to study G protein regulation of beta cell function in vivo. Proc Natl Acad Sci U S A. 2009 Nov 10;106(45):19197-202. doi: 10.1073/pnas.0906593106. Epub 2009 Oct 26. PMID: 19858481; PMCID: PMC2767362.
[9]: Jain S, Ruiz de Azua I, et,al. Chronic activation of a designer G(q)-coupled receptor improves β cell function. J Clin Invest. 2013 Apr;123(4):1750-62. doi: 10.1172/JCI66432. Epub 2013 Mar 8. PMID: 23478411; PMCID: PMC3613926.
[10]:Alexander GM, Rogan SC, et,al. Remote control of neuronal activity in transgenic mice expressing evolved G protein-coupled receptors. Neuron. 2009 Jul 16;63(1):27-39. doi: 10.1016/j.neuron.2009.06.014. PMID: 19607790; PMCID: PMC2751885.

Cas No.	34233-69-7	SDF
Sinónimos	CNO
Chemical Name	3-chloro-6-(4-methyl-4-oxidopiperazin-4-ium-1-yl)-5H-benzo[b][1,4]benzodiazepine
Canonical SMILES	C[N+]1(CCN(CC1)C2=C3C=CC=CC3=NC4=C(N2)C=C(C=C4)Cl)[O-]
Formula	C₁₈H₁₉ClN₄O	M.Wt	342.82
Solubility	≥ 17.15 mg/mL in DMSO, ≥ 49 mg/mL in Water with gentle warming This product is unstable in solution and it is recommended to prepare and use it immediately.	Storage	Store at -20°C
General tips	Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition	Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

Prepare stock solution
		1 mg	5 mg	10 mg
	1 mM	2.917 mL	14.5849 mL	29.1698 mL
	5 mM	0.5834 mL	2.917 mL	5.834 mL
	10 mM	0.2917 mL	1.4585 mL	2.917 mL

Molarity Calculator
Dilution Calculator
Molecular Weight Calculator

Calculate

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg

Average weight of animals: g

Dosing volume per animal:μL

Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.

Related Products

Reseñas

Review for Clozapine N-oxide (CNO)

Average Rating: 5 ★★★★★ (Based on Reviews and 30 reference(s) in Google Scholar.)

5 Star

100%

4 Star

0%

3 Star

0%

2 Star

0%

1 Star

0%

Review for Clozapine N-oxide (CNO)

GLPBIO products are for RESEARCH USE ONLY. Please make sure your review or question is research based.

Required fields are marked with *

Overall Rating

★

Review Title

Reseña

Apodo

Correo electrónico

You may receive emails regarding this submission. Any emails will include the ability to opt-out of future communications.

Clozapine N-oxide (CNO) (Synonyms: CNO)

Reseñas de cliente

GlpBio Citations

Bioactive Compounds Premium Provider

Product has been cited by 5 publications

Related Biological Data

Related Biological Data

Product Documents

Quality Control & SDS

Protocol

Complete Stock Solution Preparation Table

Molarity Calculator

Dilution Calculator

Molecular Weight Calculator

In vivo Formulation Calculator (Clear solution)

Related Video

Reseñas