| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
L-Type Voltage-Dependent Calcium Channels (Cav1.2, Cav1.3). Nicardipine D3 blocks L-type calcium channels in cardiac and vascular smooth muscle cells by binding to the alpha1 subunit in its inactivated state. It inhibits the influx of extracellular calcium ions (Ca2+) through these channels, leading to relaxation of coronary and peripheral arterial smooth muscle, vasodilation, reduced peripheral vascular resistance, and decreased blood pressure. Cardiac calcium channels are blocked with an IC50 of 1 uM.
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| ln Vitro |
Nicardipine blocks cardiac calcium channels with an IC50 of 1 uM in radioligand binding assays using rat cardiac membrane preparations. It is a potent vasodilator with high vascular selectivity (100-1000-fold selectivity for vascular vs. cardiac L-type calcium channels). Nicardipine also inhibits calcium-induced contraction of isolated rabbit aortic rings (IC50 = 5-10 nM). Unlike first-generation dihydropyridines, nicardipine causes less negative inotropic effect, making it safer in patients with heart failure.
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| ln Vivo |
In spontaneously hypertensive rats (SHR), oral nicardipine (3-30 mg/kg) produces dose-dependent reductions in systolic blood pressure (maximum reduction 40-50 mmHg at 3-6 hours, lasting 12-24 hours). Intravenous nicardipine (0.1-1 mg/kg) produces rapid onset of action (within 2-5 minutes) and a short duration of action (30-60 minutes). No significant reflex tachycardia is observed at antihypertensive doses due to the compound's slow onset of action and high vascular selectivity.
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| Enzyme Assay |
Radioligand binding assays are performed using membrane preparations from rat cardiac ventricles or rat brain cortex (L-type calcium channels). Membranes (100-200 microg protein) are incubated with [3H]nitrendipine (0.1-1 nM) as the radioligand and varying concentrations of nicardipine D3 (0.01-1000 nM) in 50 mM Tris-HCl buffer (pH 7.4) containing 0.01% BSA for 90 minutes at 25degC in the dark (dihydropyridines are light-sensitive). Nonspecific binding is determined with 1 microM nifedipine. Bound radioactivity is separated by rapid filtration through GF/B glass fiber filters and counted by liquid scintillation. IC50 values are calculated by nonlinear regression and converted to Ki using the Cheng-Prusoff equation.
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| Cell Assay |
Rat aortic vascular smooth muscle cells (A7r5) or human coronary artery smooth muscle cells (HCASMC) 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 45-60 minutes at 37degC. After loading, cells are washed twice with HBSS buffer and incubated with varying concentrations of nicardipine D3 (0.1 nM to 10 microM) for 30 minutes. Cells are depolarized with 50 mM KCl to open L-type calcium channels, and the fluorescence increase (excitation 494 nm, emission 516 nm) is measured in a plate reader. The IC50 for inhibition of calcium influx is calculated. Alternatively, isolated rat aortic rings are mounted in organ baths containing Krebs-Henseleit buffer (37degC, 95% O2/5% CO2). Cumulative concentration-response curves to calcium (0.1-10 mM) are generated in depolarizing buffer (60 mM KCl) in the absence or presence of nicardipine (0.1-100 nM). pA2 values are determined by Schild analysis.
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| Animal Protocol |
Male spontaneously hypertensive rats (SHR, 12-16 weeks old, 250-350 g) are anesthetized with ketamine/xylazine (80/12 mg/kg i.p.). A polyethylene catheter (PE-10) is inserted into the left carotid artery and connected to a pressure transducer for continuous blood pressure and heart rate monitoring. The left jugular vein is cannulated for drug administration. After a stabilization period (30-60 minutes), nicardipine D3 is administered intravenously as a bolus (0.1, 0.3, 1.0 mg/kg) or by infusion. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) are recorded at baseline and for 60-120 minutes post-dose. Blood samples (0.2-0.3 mL) are collected via the arterial catheter at various time points (1, 2, 5, 10, 15, 30, 45, 60, 120 minutes) for LC-MS/MS analysis of nicardipine levels. The hypotensive effect (maximum reduction in MAP, expressed as mmHg and percent change) and duration of action are calculated.
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| ADME/Pharmacokinetics |
Nicardipine D3 serves as an internal standard for LC-MS/MS bioanalysis. Nicardipine hydrochloride is well absorbed orally (bioavailability ~35% due to first-pass metabolism) but is also available intravenously. It is highly protein bound (>95%), primarily to albumin and alpha1-acid glycoprotein. Nicardipine is extensively metabolized by CYP3A4 (main pathway) and CYP2D6, with a terminal half-life of approximately 2-4 hours after oral dosing and 1-2 hours after IV administration. Steady-state is achieved within 2-3 days of oral dosing. The major metabolites (M-5, M-6) have little to no pharmacological activity. Nicardipine is eliminated in urine (60%) and feces (40%).
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| Toxicity/Toxicokinetics |
Nicardipine is generally well tolerated with a low incidence of side effects. The most common adverse reactions include headache (7%), dizziness (5%), flushing (4-10%), peripheral edema (4-7%), and palpitations (3-5%). Hypotension (2-4%) and reflex tachycardia (1-3%) may occur, particularly at higher doses. Rare but serious side effects include myocardial infarction, arrhythmias, and hepatotoxicity (elevated liver enzymes). Nicardipine can worsen heart failure in patients with reduced ejection fraction. The D3-labeled version is not intended for human use.
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| References | |
| Additional Infomation |
Nicardipine (Cardene®) was approved by the FDA in 1988 for the treatment of chronic stable angina and hypertension. The IV formulation (Cardene I.V.) is approved for short-term management of hypertension when oral therapy is not feasible. Nicardipine is also used off-label for the treatment of acute hypertensive emergencies, subarachnoid hemorrhage (to prevent vasospasm), and perioperative hypertension. The D3-labeled version is a research internal standard for LC-MS/MS bioanalysis, pharmacokinetic studies, drug-drug interaction assessments, and forensic toxicology for the precise quantification of nicardipine in biological samples.
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| Molecular Formula |
C26H27D3CLN3O6
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|---|---|
| Molecular Weight |
519.004
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| Exact Mass |
518.201
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| CAS # |
1432061-50-1
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| Related CAS # |
Nicardipine hydrochloride;54527-84-3;(S)-Nicardipine;76093-36-2;(R)-Nicardipine;76093-35-1;Nicardipine;55985-32-5
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| PubChem CID |
71750994
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| Appearance |
White to off-white 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 |
10
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| Heavy Atom Count |
36
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| Complexity |
856
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| Defined Atom Stereocenter Count |
0
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| SMILES |
[2H]C([2H])([2H])N(CCOC(=O)C1=C(NC(=C(C1C2=CC(=CC=C2)[N+](=O)[O-])C(=O)OC)C)C)CC3=CC=CC=C3.Cl
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| InChi Key |
AIKVCUNQWYTVTO-FJCVKDQNSA-N
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| InChi Code |
InChI=1S/C26H29N3O6.ClH/c1-17-22(25(30)34-4)24(20-11-8-12-21(15-20)29(32)33)23(18(2)27-17)26(31)35-14-13-28(3)16-19-9-6-5-7-10-19;/h5-12,15,24,27H,13-14,16H2,1-4H3;1H/i3D3;
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| Chemical Name |
5-O-[2-[benzyl(trideuteriomethyl)amino]ethyl] 3-O-methyl 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 |
| 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 | 1.9268 mL | 9.6339 mL | 19.2678 mL | |
| 5 mM | 0.3854 mL | 1.9268 mL | 3.8536 mL | |
| 10 mM | 0.1927 mL | 0.9634 mL | 1.9268 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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