N-Desmethylclozapine
Based on 1 Customer Validation
N-Desmethylclozapine is a major active metabolite of the atypical antipsychotic agent Clozapine. N-Desmethylclozapine is a potent, allosteric and partial M1 receptors agonist (EC50=115 nM) and is able to potentiate hippocampal N-methyl-d-aspartate (NMDA) receptor currents through M1 receptor activation. N-Desmethylclozapine is also a δ-opioid agonist.
For research use only. We do not sell to patients.
- Purity: 99.10%
- CAS No.: 6104-71-8
- Formula: C17H17ClN4
- Molecular Weight:312.80
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Purity & Documentation
- References
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Help & FAQs
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Biological Activity
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mAChR1 |
δ Opioid Receptor/DOR |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| BHK-21 | EC50 |
170 nM
Compound: 3, NDMC
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Agonist activity at human muscarinic M5 receptor expressed in BHK-21 cells assessed as increase of acetylcholine-induced calcium flux by FLIPR assay
Agonist activity at human muscarinic M5 receptor expressed in BHK-21 cells assessed as increase of acetylcholine-induced calcium flux by FLIPR assay
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[PMID: 20684563] |
| BHK-21 | EC50 |
400 nM
Compound: 3, NDMC
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Agonist activity at human muscarinic M4 receptor expressed in BHK-21 cells coexpressing Galpha16 subunit assessed as increase of acetylcholine-induced calcium flux by FLIPR assay
Agonist activity at human muscarinic M4 receptor expressed in BHK-21 cells coexpressing Galpha16 subunit assessed as increase of acetylcholine-induced calcium flux by FLIPR assay
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[PMID: 20684563] |
| CHO-K1 | EC50 |
140 nM
Compound: 3, NDMC
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Agonist activity at human muscarinic M1 receptor Y381A mutant expressed in CHO-K1 cells assessed as increase of acetylcholine-induced calcium flux by FLIPR assay
Agonist activity at human muscarinic M1 receptor Y381A mutant expressed in CHO-K1 cells assessed as increase of acetylcholine-induced calcium flux by FLIPR assay
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[PMID: 20684563] |
| CHO-K1 | EC50 |
18 nM
Compound: 3, NDMC
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Agonist activity at human muscarinic M1 receptor expressed in CHO-K1 cells assessed as increase of acetylcholine-induced calcium flux by FLIPR assay
Agonist activity at human muscarinic M1 receptor expressed in CHO-K1 cells assessed as increase of acetylcholine-induced calcium flux by FLIPR assay
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[PMID: 20684563] |
The brain penetrant metabolite N-desmethylclozapine preferentially bound to M1 muscarinic receptors with an IC50 of 55 nM and was a more potent partial agonist (EC50, 115 nM and 50% of acetylcholine response) at this receptor than clozapine[1].
N-desmethylclozapine exhibits slight agonistic effects on the M1 mAChR, and agonistic properties at the 5-HT1A receptor in the cerebral cortex and hippocampus. This compound also behaves as an agonist at the δ-opioid receptor in the cerebral cortex and striatum[2].
N-desmethylclozapine (3 μM) greatly decreases the outward current in excitatory neurons, but not in inhibitory neurons. In excitatory neurons, N-desmethylclozapine alone is more effective than either clozapine alone or the combination of clozapine and N-desmethylclozapine. The effect of N-desmethylclozapine in excitatory neurons is significantly suppressed by 0.1 μM pirenzepine and 1 μM atropine. N-desmethylclozapine, but not clozapine, suppressed K+ channels via M1 receptors in excitatory cells[3].
N-desmethylclozapine leads to a decrease in TxB2 levels under unstimulated conditions as well as under TSST-1 stimulation. Clozapine, N-desmethylclozapine and CPZ possibly act on neurotransmitter systems via modulation of TxA2 or TxB2 production[5].
The IC50s of N-desmethylclozapine, fluoxetine hydrochloride, and salmeterol xinafoate in Huh-7 cells infected with DENV-2 are 1 μM, 0.38 μM, and 0.67 μM, respectively. The levels of NS3 are reduced in cells treated with all three inhibitors compared to DMSO treatment, suggesting that the inhibitors act at a stage prior to viral protein translation. N-Desmethylclozapine-treated cells show a >75% reduction in negative-strand RNA levels[6].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Chemical Information
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CAS No. 6104-71-8
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Appearance Solid
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Molecular Weight 312.80
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Formula C17H17ClN4
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Color Light yellow to green yellow
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SMILES
ClC1=CC=C2C(N=C(N3CCNCC3)C4=CC=CC=C4N2)=C1
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Synonyms
Norclozapine; Desmethylclozapine; Normethylclozapine
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Solvent & Solubility
DMSO : ≥ 50 mg/mL (159.85 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
* "≥" means soluble, but saturation unknown.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (7.99 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (7.99 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation
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Data Sheet (281 KB)
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SDS (454 KB)
- English - EN (454 KB)
- Français - FR (454 KB)
- Deutsch - DE (454 KB)
- Norwegian - NO (454 KB)
- Español - ES (454 KB)
- Swedish - SV (454 KB)
- Italian - IT (454 KB)
- Korean - KR (454 KB)
- Portuguese - PT (454 KB)
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Handling Instructions (2659 KB)
References
[1]. Li Z, et al. N-desmethylclozapine, a major metabolite of clozapine, increases cortical acetylcholine and dopamine release in vivo via stimulation of M1 muscarinic receptors. Neuropsychopharmacology. 2005 Nov;30(11):1986-95. [Content Brief]
[2]. Odagaki Y, et al. Comparative analysis of pharmacological properties of xanomeline and N-desmethylclozapine in rat brain membranes. J Psychopharmacol. 2016 Sep;30(9):896-912 [Content Brief]
[3]. Sugawara Y, et al. Electrophysiological evidence showing muscarinic agonist-antagonist activities of N-desmethylclozapine using hippocampal excitatory and inhibitory neurons. Brain Res. 2016 Jul 1;1642:255-62 [Content Brief]
[4]. Gigout S, et al. Different pharmacology of N-desmethylclozapine at human and rat M2 and M 4 mAChRs in neocortex. Naunyn Schmiedebergs Arch Pharmacol. 2015 May;388(5):487-96 [Content Brief]
[5]. Himmerich H, et al. Impact of clozapine, N-desmethylclozapine and chlorpromazine on thromboxane production in vitro. Med Chem. 2012 Nov;8(6):1032-8. [Content Brief]
[6]. Medigeshi GR, et al. N-Desmethylclozapine, Fluoxetine and Salmeterol inhibit post-entry stages of dengue virus life-cycle. Antimicrob Agents Chemother. 2016 Aug 29. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 3.1969 mL | 15.9847 mL | 31.9693 mL | 79.9233 mL |
| 5 mM | 0.6394 mL | 3.1969 mL | 6.3939 mL | 15.9847 mL | |
| 10 mM | 0.3197 mL | 1.5985 mL | 3.1969 mL | 7.9923 mL | |
| 15 mM | 0.2131 mL | 1.0656 mL | 2.1313 mL | 5.3282 mL | |
| 20 mM | 0.1598 mL | 0.7992 mL | 1.5985 mL | 3.9962 mL | |
| 25 mM | 0.1279 mL | 0.6394 mL | 1.2788 mL | 3.1969 mL | |
| 30 mM | 0.1066 mL | 0.5328 mL | 1.0656 mL | 2.6641 mL | |
| 40 mM | 0.0799 mL | 0.3996 mL | 0.7992 mL | 1.9981 mL | |
| 50 mM | 0.0639 mL | 0.3197 mL | 0.6394 mL | 1.5985 mL | |
| 60 mM | 0.0533 mL | 0.2664 mL | 0.5328 mL | 1.3321 mL | |
| 80 mM | 0.0400 mL | 0.1998 mL | 0.3996 mL | 0.9990 mL | |
| 100 mM | 0.0320 mL | 0.1598 mL | 0.3197 mL | 0.7992 mL |
N-Desmethylclozapine Related Classifications
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