| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
Serotonin Transporter (SERT), Norepinephrine Transporter (NET), and Dopamine Transporter (DAT). Clomipramine D3 HCl acts as a potent and relatively selective serotonin reuptake inhibitor (SSRI) while also blocking the norepinephrine and dopamine transporters, albeit with lower affinity. It blocks radioligand binding to human SERT, NET, and DAT with Ki values of 0.14 nM, 54 nM, and 3 nM, respectively. It also has anticholinergic (muscarinic receptor antagonist) and antihistaminergic (H1) properties.
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| ln Vitro |
Clomipramine potently inhibits [3H]5-HT uptake in rat brain synaptosomes (IC50 = 1.5 nM). It is a more potent inhibitor of 5-HT uptake than of norepinephrine uptake (IC50 = 35 nM for NE). The D3-labeled form is assumed to have identical receptor binding and transporter inhibition properties, making it an ideal analytical tracer. It induces apoptosis in various cancer cell lines at high concentrations (IC50 20-100 uM).
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| ln Vivo |
In animal models of depression (e.g., forced swim test, FST), clomipramine (10-30 mg/kg i.p.) significantly reduces immobility time in mice and rats, indicating antidepressant-like activity. In a rat model of obsessive-compulsive disorder (OCD), chronic clomipramine (10-20 mg/kg/day for 14-21 days) reduces perseverative behaviors (e.g., marble burying, lever pressing). The D3-labeled form is used as an IS in PK studies measuring drug exposure.
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| Enzyme Assay |
Radioligand binding assays are performed using membrane preparations from CHO or HEK-293 cells expressing human SERT, NET, or DAT. Membranes (20-50 microg protein) are incubated with [3H]paroxetine (for SERT) or [3H]nisoxetine (for NET) or [3H]WIN35,428 (for DAT) as radioligands, and varying concentrations of Clomipramine D3 HCl (0.01-1000 nM) in 50 mM Tris-HCl buffer (pH 7.4) containing 120 mM NaCl and 5 mM KCl for 60 min at 25degC. Nonspecific binding is determined with excess cold ligand (e.g., 10 uM fluoxetine). Bound radioactivity is separated by GF/B filtration.
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| Cell Assay |
Rat brain synaptosomes (P2 fraction) are prepared from cerebral cortex. Aliquots (50-100 ug protein) are incubated in Krebs-Henseleit buffer (pH 7.4) containing 10 uM pargyline (MAO inhibitor), 0.1% ascorbic acid, and varying concentrations of Clomipramine D3 HCl (0.1-1000 nM) for 10 min at 37degC. Uptake is initiated by adding [3H]5-HT or [3H]NE (final concentration 10-50 nM). After 5-10 min, uptake is terminated by rapid filtration through GF/B filters. Filters are washed, and accumulated radioactivity is counted. IC50 values are calculated.
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| Animal Protocol |
Male Sprague-Dawley rats (200-250 g) are surgically implanted with a microdialysis probe in the frontal cortex or dorsal raphe nucleus. After 24-48 h recovery, aCSF is perfused (1.5 uL/min). After baseline stabilization (3-4 samples), Clomipramine (10-20 mg/kg) or vehicle is administered i.p. Dialysates are collected every 20 min for 2-3 h. 5-HT, NE, and DA levels are quantified by HPLC-ECD. Changes in neurotransmitter levels are expressed as percent of baseline. Clomipramine D3 may be added to aCSF for intra-probe delivery.
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| ADME/Pharmacokinetics |
Clomipramine D3 HCl serves as an internal standard (IS) for LC-MS/MS quantification. The parent drug clomipramine is well absorbed orally (bioavailability ~50-60%), with a terminal half-life of ~20-25 h in humans. It is highly protein bound (>95%), extensively metabolized by CYP2D6 and CYP3A4 to its primary active metabolite, N-desmethylclomipramine (norclomipramine). The D3-labeled IS has near-identical extraction efficiency and ionization properties.
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| Toxicity/Toxicokinetics |
The D3-labeled version is not for human use. Clomipramine shares the general TCA toxicity profile: common AEs include dry mouth, constipation, urinary retention (anticholinergic), drowsiness, weight gain, and orthostatic hypotension. Serious AEs: cardiotoxicity (QT prolongation, arrhythmia), seizures (especially at high doses), and increased suicidality in children/adolescents. Overdose can be fatal.
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| References |
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| Additional Infomation |
Clomipramine (Anafranil) was FDA-approved in 1989 for the treatment of obsessive-compulsive disorder (OCD). It is considered the gold standard pharmacological therapy for OCD. The D3-labeled version is a research internal standard for LC-MS/MS bioanalysis in therapeutic drug monitoring (TDM) of clomipramine, drug-drug interaction studies, and pharmacogenetic studies investigating CYP2D6 and CYP3A4 polymorphisms that influence its metabolism and clinical response.
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| Molecular Formula |
C19H24CL2N2
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|---|---|
| Molecular Weight |
354.331748008728
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| Exact Mass |
353.15
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| CAS # |
1398065-86-5
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| Related CAS # |
Clomipramine hydrochloride;17321-77-6;Clomipramine-d3;136765-29-2
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| PubChem CID |
121225399
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| Appearance |
White to off-white solid powder
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| Flash Point |
9℃
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
23
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| Complexity |
346
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| Defined Atom Stereocenter Count |
0
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| SMILES |
[2H]C([2H])([2H])N(C)CCCN1C2=CC=CC=C2CCC3=C1C=C(C=C3)Cl.Cl
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| InChi Key |
WIMWMKZEIBHDTH-NIIDSAIPSA-N
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| InChi Code |
InChI=1S/C19H23ClN2.ClH/c1-21(2)12-5-13-22-18-7-4-3-6-15(18)8-9-16-10-11-17(20)14-19(16)22;/h3-4,6-7,10-11,14H,5,8-9,12-13H2,1-2H3;1H/i1D3;
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| Chemical Name |
3-(2-chloro-5,6-dihydrobenzo[b][1]benzazepin-11-yl)-N-methyl-N-(trideuteriomethyl)propan-1-amine;hydrochloride
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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, avoid exposure to moisture. |
| 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 : ~125 mg/mL (~352.78 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.87 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 20.8 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: ≥ 2.08 mg/mL (5.87 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 20.8 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (5.87 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8222 mL | 14.1111 mL | 28.2223 mL | |
| 5 mM | 0.5644 mL | 2.8222 mL | 5.6445 mL | |
| 10 mM | 0.2822 mL | 1.4111 mL | 2.8222 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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