| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
Noradrenaline Transporter (NET), Serotonin Transporter (SERT), and Dopamine Transporter (DAT). N-Desmethyl clomipramine acts as a dual reuptake inhibitor, but preferentially inhibits the norepinephrine transporter (NET) more potently than clomipramine. It blocks the reuptake of norepinephrine and serotonin by binding to their respective transporters, increasing synaptic neurotransmitter concentrations, and possesses its own antidepressant activity.
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| ln Vitro |
The metabolite inhibits [3H]norepinephrine uptake in rat brain synaptosomes with an IC50 of approximately 10-20 nM, showing higher noradrenergic selectivity than the parent drug, while its 5-HT reuptake inhibition is weaker (IC50 ~40 nM). It has a Ki of 54 nM for NET and 0.14 nM for SERT, respectively, for radioligand binding.
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| ln Vivo |
In rat models, desmethylclomipramine (1-10 mg/kg i.p.) effectively reverses reserpine-induced hypothermia and potentiates the pressor response to tyramine, confirming its NET occupancy. In non-human primates, PET studies with (S,S)-[¹⁸F]FMeNER-D2 demonstrate significant in vivo NET occupancy at therapeutic doses, with the metabolite likely contributing to the overall antidepressant effect.
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| Enzyme Assay |
Radioligand binding assays are performed using membrane preparations from HEK-293 or CHO cells expressing human NET or SERT. Membranes (50 microg protein) are incubated with [3H]nisoxetine (for NET) or [3H]paroxetine (for SERT) and varying concentrations of N-Desmethyl Clomipramine HCl in Tris-HCl buffer for 60 min at 25degC. Non-specific binding is determined using 10 microM desipramine or fluoxetine. Bound radioactivity is separated by GF/B filter filtration and measured by liquid scintillation.
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| Cell Assay |
Rat brain cortical slices are prepared and pre-incubated in oxygenated Krebs buffer at 37degC. Varying concentrations of the test compound are added, followed by [3H]norepinephrine or [3H]5-HT. After a 10-min incubation, the uptake is terminated by rapid washing, the slices are solubilized, and the accumulated radioactivity is quantified by liquid scintillation. The IC50 for inhibition of neurotransmitter uptake is calculated.
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| Animal Protocol |
Male Sprague-Dawley rats (200-250 g) are anesthetized, the femoral artery is cannulated for blood pressure monitoring, and the femoral vein for drug administration. After baseline stabilization, the animals are treated with N-Desmethyl Clomipramine (1-5 mg/kg i.v.) or vehicle. NET occupancy in vivo is assessed by displacement of a selective PET radioligand (e.g., (S,S)-[¹⁸F]FMeNER-D2), and the animals are sacrificed for brain sectioning and autoradiography analysis.
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| ADME/Pharmacokinetics |
N-Desmethyl clomipramine is a major human metabolite, primarily formed by CYP2D6 and CYP3A4-mediated demethylation. In humans, the metabolite has a long elimination half-life (approximately 20-40 hours), which may be longer than that of the parent drug (clomipramine ~20-25 h). It is highly protein bound (>95%) and accumulates in the brain, contributing to the net pharmacological effect.
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| Toxicity/Toxicokinetics |
The toxicity profile is similar to other TCAs; however, N-Desmethyl clomipramine is considered less cardiotoxic than the parent drug due to reduced sodium channel blockade. High systemic exposure may still cause anticholinergic side effects (dry mouth, urinary retention, constipation) and CNS depression, seizures, or cardiac conduction abnormalities at supratherapeutic levels.
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| References |
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| Additional Infomation |
Clomipramine (Anafranil) was FDA-approved in 1989 for obsessive-compulsive disorder (OCD). N-Desmethyl clomipramine is primarily a research tool and analytical reference standard. It is used in bioanalytical assays (LC-MS/MS) for pharmacokinetic studies, therapeutic drug monitoring, and to understand genetic polymorphisms in CYP2D6 that affect the metabolic ratio and clinical response.
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| Molecular Formula |
C₁₈H₂₂CL₂N₂
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|---|---|
| Molecular Weight |
337.29
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| Exact Mass |
336.116
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| CAS # |
29854-14-6
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| Related CAS # |
N-Desmethyl Clomipramine-d3 hydrochloride;1189971-04-7
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| PubChem CID |
16219718
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| Appearance |
White to off-white solid powder
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| Boiling Point |
466ºC at 760 mmHg
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| Melting Point |
204-206°C (dec.)
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| Flash Point |
235.6ºC
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| Vapour Pressure |
4.41E-09mmHg at 25°C
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| LogP |
5.444
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
22
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| Complexity |
322
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
KMDDAZOLOSKTKZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H21ClN2.ClH/c1-20-11-4-12-21-17-6-3-2-5-14(17)7-8-15-9-10-16(19)13-18(15)21;/h2-3,5-6,9-10,13,20H,4,7-8,11-12H2,1H3;1H
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| Chemical Name |
3-(2-chloro-5,6-dihydrobenzo[b][1]benzazepin-11-yl)-N-methylpropan-1-amine;hydrochloride
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| Synonyms |
NDesmethyl Clomipramine HCl; N Desmethyl Clomipramine HCl
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~25 mg/mL (~74.12 mM)
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9648 mL | 14.8240 mL | 29.6481 mL | |
| 5 mM | 0.5930 mL | 2.9648 mL | 5.9296 mL | |
| 10 mM | 0.2965 mL | 1.4824 mL | 2.9648 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.
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.
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