Clozapine N-oxide diHCl

Alias: Clozapine Noxide diHCl; Clozapine N oxide diHCl; Clozapine N-oxide dihydrochloride
Cat No.:V38749 Purity: ≥98%
Clozapine N-oxide diHCl is a major metabolite of Clozapine which is an antipsychotic acting as an antagonist of dopamine and other receptors such as muscarinic M1 receptor.
Clozapine N-oxide diHCl Chemical Structure CAS No.: 2250025-93-3
Product category: mAChR
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
25mg
50mg
100mg
250mg
Other Sizes

Other Forms of Clozapine N-oxide diHCl:

  • Clozapine N-oxide
Official Supplier of:
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Top Publications Citing lnvivochem Products
Product Description

Clozapine N-oxide diHCl is a major metabolite of Clozapine which is an antipsychotic acting as an antagonist of dopamine and other receptors such as muscarinic M1 receptor.

Biological Activity I Assay Protocols (From Reference)
Targets
mAChR4; mAChR3
ln Vitro
Zapine N-oxide (CNO) can be combined with non-DREADD absorption at the concentrations required for DREADD activation and undergo chloride reversal to decrypt the parent compound chloride, an atypical antipsychotic that acts on many pharmacological targets and produce a variety of physiological and behavioral effects [2].
ln Vivo
Clozapine N-oxide dihydrochloride (CNO) network levels at 15 min after a single intraperitoneal (ip) injection of clozapine N-oxide dihydrochloride (1 mg/kg) into mice Highest, very low after 2 hours. Axial half-life in mice is quiescent, but biological effects have been described after rapid handling of experimental animals expressing DREADD, often over long periods of time (6-10 hours) [1].
References

[1]. Novel designer receptors to probe GPCR signaling and physiology. Trends Pharmacol Sci. 2013 Jul;34(7):385-92.

[2]. 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.

[3]. Gram scale preparation of clozapine N-oxide (CNO), a synthetic small molecule actuator for muscarinic acetylcholine DREADDs. MethodsX. 2018 Mar 23;5:257-267.

[4]. Branch-specific dendritic Ca(2+) spikes cause persistent synaptic plasticity. Nature. 2015 Apr 9;520(7546):180-5.

[5]. 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.

[6]. Clozapine is a potent and selective muscarinic M4 receptor agonist. Eur J Pharmacol. 1994 Nov 15;269(3):R1-2.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C₁₈H₂₁CL₃N₄O
Molecular Weight
415.74
Exact Mass
414.08
CAS #
2250025-93-3
Related CAS #
Clozapine N-oxide; 34233-69-7
Appearance
Solid
SMILES
C[N+]1(CCN(CC1)C2=NC3=C(C=CC(=C3)Cl)NC4=CC=CC=C42)[O-].Cl.Cl
InChi Key
MBRGKRXDVKTUPT-UHFFFAOYSA-N
InChi Code
InChI=1S/C18H19ClN4O.2ClH/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;2*1H
Chemical Name
3-chloro-6-(4-methyl-4-oxidopiperazin-4-ium-1-yl)-11H-benzo[b][1,4]benzodiazepine;dihydrochloride
Synonyms
Clozapine Noxide diHCl; Clozapine N oxide diHCl; Clozapine N-oxide dihydrochloride
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: ~240 mg/mL (~577.3 mM)
H2O: ~100 mg/mL (~240.5 mM)
Solubility (In Vivo)
Solubility in Formulation 1: ≥ 6 mg/mL (14.43 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 60.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

Solubility in Formulation 2: ≥ 6 mg/mL (14.43 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 60.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 2.4053 mL 12.0267 mL 24.0535 mL
5 mM 0.4811 mL 2.4053 mL 4.8107 mL
10 mM 0.2405 mL 1.2027 mL 2.4053 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

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What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
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Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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Calculation results

Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
             (2) Be sure to add the solvent(s) in order.

Biological Data
  • Docking of clozapine-N-oxide (CNO) into the ligand binding pocket of the rat M3 muscarinic receptor (M3R). Trends Pharmacol Sci . 2013 Jul;34(7):385-92.
  • CNO produces clozapine-like interoceptive stimulus effects in standard laboratory rats and mice. Sci Rep . 2018 Mar 1;8(1):3840.
  • CNO is converted to clozapine in standard laboratory rats and mice. Sci Rep . 2018 Mar 1;8(1):3840.
  • ORTEP representation of the molecular structure of CNO. MethodsX . 2018 Mar 23:5:257-267.
  • Activation profiles of CNO and clozapine at the M1 DREADD. MethodsX . 2018 Mar 23:5:257-267.
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