| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
L-Type Voltage-Dependent Calcium Channels (Cav1.2). (R)-Lercanidipine D3 blocks L-type voltage-dependent calcium channels in vascular smooth muscle cells. By binding to the alpha1 subunit of the channel in its inactivated state, it prevents calcium ion influx, leading to reduced intracellular calcium, relaxation of arterial smooth muscle, vasodilation, and decreased peripheral vascular resistance, resulting in lowered blood pressure.
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| ln Vitro |
(R)-Lercanidipine exhibits high affinity for L-type calcium channels with an IC50 of approximately 1-3 nM in radioligand binding assays using rat cardiac membranes. It is more potent than the (S)-enantiomer and shows high vascular selectivity with less negative inotropic effect on cardiac muscle compared to first-generation dihydropyridines such as nifedipine.
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| ln Vivo |
In spontaneously hypertensive rats (SHR), oral administration of (R)-lercanidipine (1-10 mg/kg) produces dose-dependent and long-lasting (24-48 hours) reductions in systolic and diastolic blood pressure. The maximum antihypertensive effect (30-40 mmHg reduction) is observed 2-4 hours post-dose. Unlike older CCBs, it causes minimal reflex tachycardia due to its slow onset and long duration of action.
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| Enzyme Assay |
Radioligand binding assays are performed using membrane preparations from rat cardiac ventricles or human recombinant Cav1.2 channels expressed in CHO cells. Membranes (40-80 microg protein) are incubated with [3H]nitrendipine as the radioligand and varying concentrations of (R)-lercanidipine D3 in 50 mM Tris-HCl buffer (pH 7.4) containing 0.01% BSA for 90 minutes at 25degC in the dark. Nonspecific binding is determined with 1 microM nifedipine. Bound and free radioligands are separated by filtration through GF/B filters, and bound radioactivity is measured by liquid scintillation counting. IC50 values are converted to Ki using the Cheng-Prusoff equation.
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| Cell Assay |
Rat aortic vascular smooth muscle cells (A7r5) are cultured in DMEM with 10% FBS. Cells are seeded in 96-well plates (50,000 cells/well) for 24 hours, then loaded with the calcium-sensitive fluorescent dye Fluo-4 AM (5 microM) for 60 minutes at 37degC. After washing, cells are pre-incubated with varying concentrations of (R)-lercanidipine D3 for 30 minutes, then depolarized with 50 mM KCl to activate L-type calcium channels, and intracellular calcium increases are measured by fluorescence (excitation at 494 nm, emission at 516 nm) using a plate reader. IC50 values are calculated from the inhibition of the KCl-induced calcium signal.
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| Animal Protocol |
Male spontaneously hypertensive rats (SHR, 250-350 g, 12-16 weeks old) are used. Animals are anesthetized with isoflurane, and a telemetry transmitter is implanted into the abdominal aorta for continuous blood pressure monitoring. After 7 days recovery, rats receive a single oral dose of (R)-lercanidipine (1-10 mg/kg) or vehicle. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) are recorded continuously for 48 hours post-dose. Blood samples are collected from the tail vein at various time points for LC-MS/MS analysis of drug concentrations to determine pharmacokinetic parameters.
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| ADME/Pharmacokinetics |
(R)-Lercanidipine D3 serves as an internal standard for bioanalytical quantification of lercanidipine. The parent drug lercanidipine is highly lipophilic, has an oral bioavailability of approximately 10-20% due to extensive first-pass metabolism, and is >98% bound to plasma proteins (albumin and alpha1-acid glycoprotein). It has a terminal half-life of 8-10 hours, and the antihypertensive effect lasts for 24 hours, supporting once-daily dosing.
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| Toxicity/Toxicokinetics |
Lercanidipine is well tolerated with a low incidence of typical dihydropyridine side effects. Common adverse reactions include headache, dizziness, ankle edema, flushing, and palpitations (2-5% incidence). Gingival hyperplasia (0.5-1%) and rash are less common. It has a lower risk of causing reflex tachycardia or negative inotropic effects compared to nifedipine. The R-enantiomer is the clinically active form.
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| References | |
| Additional Infomation |
Lercanidipine was approved in Europe in 1997 and in the US in 2023 (Zanidip®) for the treatment of essential hypertension. It is a third-generation CCB with long-acting, highly vascular-selective properties that reduce the incidence of adverse effects. The D3-labeled version is a research internal standard for LC-MS/MS bioanalysis, drug-drug interaction studies, and pharmacokinetic research.
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| Molecular Formula |
C36H39D3CLN3O6
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|---|---|
| Molecular Weight |
651.207
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| Exact Mass |
650.295
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| CAS # |
1217724-52-1
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| Related CAS # |
(R)-Lercanidipine hydrochloride;187731-34-6
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| PubChem CID |
46782045
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| Appearance |
Light yellow to yellow solid powder
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
13
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| Heavy Atom Count |
46
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| Complexity |
1090
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1(C)=C(C(OC)=O)[C@@H](C2C=CC=C([N+]([O-])=O)C=2)C(C(=O)OC(C)(C)CN(C([2H])([2H])[2H])CCC(C2C=CC=CC=2)C2C=CC=CC=2)=C(C)N1.Cl
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| InChi Key |
WMFYOYKPJLRMJI-UUOWBLICSA-N
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| InChi Code |
InChI=1S/C36H41N3O6.ClH/c1-24-31(34(40)44-6)33(28-18-13-19-29(22-28)39(42)43)32(25(2)37-24)35(41)45-36(3,4)23-38(5)21-20-30(26-14-9-7-10-15-26)27-16-11-8-12-17-27;/h7-19,22,30,33,37H,20-21,23H2,1-6H3;1H/t33-;/m1./s1/i5D3;
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| Chemical Name |
5-O-[1-[3,3-diphenylpropyl(trideuteriomethyl)amino]-2-methylpropan-2-yl] 3-O-methyl (4R)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate;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 | 1.5356 mL | 7.6780 mL | 15.3560 mL | |
| 5 mM | 0.3071 mL | 1.5356 mL | 3.0712 mL | |
| 10 mM | 0.1536 mL | 0.7678 mL | 1.5356 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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