| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
Diltiazem-d3 hydrochloride targets L-type voltage-gated calcium channels, specifically the Ca2+ influx pathway in cardiac and vascular smooth muscle cells. Diltiazem is a benzothiazepine-class calcium channel blocker that inhibits calcium influx through slow channels, reducing cardiac contractility and causing vasodilation. The compound shows antihypertensive and antiarrhythmic effects. The deuterium labeling does not alter the target specificity, as the isotopic substitution is at the N-methyl position and does not affect receptor binding.
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| ln Vitro |
Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as quantitative tracers while the drugs were being developed. Because deuteration may have an effect on a drug's pharmacokinetics and metabolic properties, it is a cause for concern [1].
In vitro, diltiazem inhibits Ca2+ influx through L-type calcium channels in a concentration-dependent manner. The compound reduces intracellular calcium levels in cardiomyocytes and vascular smooth muscle cells, leading to decreased contractility and vasodilation. Diltiazem-d3 exhibits similar in vitro activity to the non-labeled parent compound, with the isotopic substitution primarily affecting analytical detection rather than biological activity. Standard in vitro assays include patch-clamp electrophysiology on cardiomyocytes or cell lines expressing L-type calcium channels, as well as functional assays measuring calcium influx using fluorescent indicators. |
| ln Vivo |
In vivo, diltiazem demonstrates antihypertensive, antianginal, and antiarrhythmic effects. It reduces blood pressure by causing vasodilation and decreases cardiac oxygen demand by reducing heart rate and contractility. Diltiazem is used clinically for the treatment of cardiac arrhythmia, hypertension, and angina pectoris. The deuterium labeling in diltiazem-d3 is not expected to significantly alter the in vivo pharmacological profile compared to the parent compound, though deuteration can potentially affect pharmacokinetic and metabolic profiles.
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| Enzyme Assay |
For non-cell-based receptor binding assays, diltiazem-d3 can be evaluated using membrane preparations from tissues expressing L-type calcium channels. Radioligand binding displacement experiments are performed using a radiolabeled calcium channel ligand such as [3H]-diltiazem or [3H]-nitrendipine. Membrane homogenates are incubated with increasing concentrations of the test compound and a fixed concentration of the radioligand at room temperature for 1-2 hours. Bound radioligand is separated from free by rapid filtration through GF/B filters. Nonspecific binding is determined in the presence of excess unlabeled diltiazem. IC50 or Ki values are calculated from displacement curves using nonlinear regression analysis.
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| Cell Assay |
For in vitro cellular assays, cardiomyocytes or cell lines expressing L-type calcium channels are cultured in appropriate medium and plated in multi-well plates. Cells are loaded with a calcium-sensitive fluorescent dye such as Fluo-4 AM or Fura-2 AM. After dye loading and washing, cells are pre-incubated with various concentrations of diltiazem-d3 for 15-30 minutes. Calcium influx is stimulated by the addition of a depolarizing agent such as high potassium buffer. Fluorescence intensity is measured using a fluorescence plate reader or imaging system. The reduction in calcium signal compared to control wells is used to calculate the IC50 value. Patch-clamp electrophysiology can also be employed for direct measurement of channel current inhibition.
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| Animal Protocol |
For in vivo animal studies, diltiazem-d3 can be administered to animal models via oral gavage or intravenous injection. In spontaneously hypertensive rats, blood pressure is monitored via tail-cuff or telemetry following compound administration. In models of cardiac arrhythmia, ECG is recorded to assess antiarrhythmic effects. In angina models, exercise tolerance and ST-segment changes are evaluated. For pharmacokinetic studies, blood samples are collected at predetermined time points post-administration for LC-MS/MS analysis. Dosing regimens are typically based on the parent compound's established pharmacology.
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| ADME/Pharmacokinetics |
As a deuterium-labeled compound, diltiazem-d3 is primarily used as an analytical standard rather than for therapeutic pharmacokinetic studies. Deuteration can alter the pharmacokinetic profile of drugs by affecting metabolic stability, potentially reducing the rate of metabolism and extending half-life. The parent compound diltiazem has an oral bioavailability of approximately 40%, is highly protein-bound (70-80%), and has a half-life of 3-4.5 hours. It is metabolized by CYP3A4 in the liver. Diltiazem-d3 would be expected to have similar absorption and distribution characteristics, with the deuterium atoms potentially slowing CYP450-mediated metabolism.
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| Toxicity/Toxicokinetics |
The toxicity profile of diltiazem-d3 is expected to be similar to that of the parent compound diltiazem. Diltiazem has a well-established safety profile in clinical use, with common adverse effects including dizziness, headache, edema, and hypotension. Serious adverse effects include bradycardia, atrioventricular block, and heart failure exacerbation. The deuterium substitution is not expected to introduce new toxicities, as deuterium is a stable, non-radioactive isotope of hydrogen that is generally considered safe for research and pharmaceutical applications. Standard safety pharmacology studies would include assessment of cardiovascular, respiratory, and central nervous system effects.
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| References |
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| Additional Infomation |
Diltiazem-d3 hydrochloride is the deuterium-labeled form of diltiazem hydrochloride, a calcium channel blocker used clinically for the treatment of cardiac arrhythmia, hypertension, and angina pectoris. Diltiazem was first approved by the FDA in 1982 and is available in various formulations including oral tablets and intravenous preparations. Diltiazem-d3 is used primarily as an internal standard in LC-MS/MS methods for the quantification of diltiazem in biological samples. The compound is for research use only and not for human consumption. The mechanism of action involves L-type calcium channel blockade, leading to vasodilation and reduced cardiac contractility.
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| Molecular Formula |
C22H24D3CLN2O4S
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| Molecular Weight |
454.00
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| Exact Mass |
453.156
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| CAS # |
1217623-80-7
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| Related CAS # |
Diltiazem hydrochloride;33286-22-5
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| PubChem CID |
45039052
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| Appearance |
White to off-white solid powder
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| Melting Point |
197-200°C
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
30
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| Complexity |
565
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| Defined Atom Stereocenter Count |
2
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| SMILES |
[2H]C([2H])([2H])N(C)CCN1C2=CC=CC=C2S[C@H]([C@H](C1=O)OC(=O)C)C3=CC=C(C=C3)OC.Cl
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| InChi Key |
HDRXZJPWHTXQRI-ZOFGQJPPSA-N
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| InChi Code |
InChI=1S/C22H26N2O4S.ClH/c1-15(25)28-20-21(16-9-11-17(27-4)12-10-16)29-19-8-6-5-7-18(19)24(22(20)26)14-13-23(2)3;/h5-12,20-21H,13-14H2,1-4H3;1H/t20-,21+;/m1./s1/i2D3;
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| Chemical Name |
[(2S,3S)-2-(4-methoxyphenyl)-5-[2-[methyl(trideuteriomethyl)amino]ethyl]-4-oxo-2,3-dihydro-1,5-benzothiazepin-3-yl] acetate;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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 2.2026 mL | 11.0132 mL | 22.0264 mL | |
| 5 mM | 0.4405 mL | 2.2026 mL | 4.4053 mL | |
| 10 mM | 0.2203 mL | 1.1013 mL | 2.2026 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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