| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
Benidipine (also known as SC-278724, KW-3049 and Coniel) is a potent and long acting dihydropyridine calcium channel blocker used to treat hypertension and angina pectoris. It also inhibits aldosterone-induced MCR activation.In addition, benidipine Hydrochloride has been reported to reduce oxidative stress.Benidipineis sold in the United States under the proprietary name Sular. Nisoldipine has tropism for cardiac blood vessels.
| ln Vivo |
Significant anti-apoptotic effects are shown by benidipine (3, 5, 10 µg/kg; intravenously) in a hemodynamically independent way [2]. In hypertensive rats, benidipine (5 mg/kg) administered intravenously every other day for six weeks improves coronary circulation and enhances endothelial nitric oxide synthase (eNOS) activity [3]. On ischemia-reperfusion injury, benidipine (1, 3, 10 mg/kg); oral; once daily for 1 week [4] has a strong cardioprotective effect.
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| Animal Protocol |
Animal/Disease Models: Sham MI (myocardial ischemia)/R (ischemia-reperfusion injury) rabbit and MI/R rabbit [2]
Doses: 3, 5, 10 µg/kg Route of Administration: intravenous (iv) (iv)injection Experimental Results:Causes HR (heart rate ) Dramatically diminished MABP (mean arterial blood pressure), PRI (pressure rate index) at 10 µg/kg, and apoptosis-positive cells were diminished to 7.4% at 3 µg/kg, which was not consistent with the results observed in the higher dose treatment group. Significant differences. Animal/Disease Models: Renovascular Hypertensive Rat (RHR) [3] Doses: 5 mg/kg (dissolved in peanut oil) Route of Administration: intravenous (iv) (iv)injection; once every other day for 6 weeks Experimental Results: Significant reduction in blood pressure and coronary artery disease Vascular resistance index, but increased nitrite production and eNOS mRNA expression, Dramatically increased resting coronary flow and capillary density. Animal/Disease Models: Rat (cardiac model (Langendorff perfusion)) [4] Doses: 1, 3, 10 mg/kg Route of Administration: Po; one time/day for 1 wee |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
Benidipine is rapidly absorbed after oral administration reaching a maximum concentration within 2 hours. The short period of time needed for maximum concentration to get reached is a particular characteristic of benidipine when compared with other calcium channel blockers. The registered maximum concentration and AUC are dose-dependent and it can go from 0.55-3.89 ng/ml and 1.04-6.7 ng.h/ml respectively when administered in a dose of 2-8 mg. The percentage of urinary excretion after oral administration is of approximate 36% of the administered dose. Most of the remaining dose is excreted in feces, making bile excretion the major elimination pathway of benidipine. From the eliminated drug, none of it is expressed in the form of the unchanged drug. Benidipine is highly distributed to the tissues mainly in the liver and kidneys and plasma. It does not present a high accumulation following repeated oral administrations. Metabolism / Metabolites Benidipine is almost completely metabolized in the liver. From different reports, it is thought that benidipine is mainly metabolized by CYP3A. Some of the formed metabolites are N-desbenzylbenidipine and dehydrobenidipine. Analysis on the formation of metabolites has indicated that the metabolism is mainly performed by CYP3A4 and CYP3A5. Biological Half-Life The elimination half-life of benidipine is registered to be of approximate 1 hour. |
| Toxicity/Toxicokinetics |
Protein Binding
Benidipine is highly bound to plasma proteins and the bound form can account for even 98% of the administered dose. |
| References |
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| Additional Infomation |
Benidipine has the formula 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid methyl 1-(phenylmethyl)-3-piperidinyl ester hydrochloride. It is a synthetic dihydropyridine derivative that has anti-hypertensive and anti-anginal actions. It was originated in Japan by Kyowa Hakko, it is submitted for FDA approval and it is currently available in some Asian countries like India and Japan.
Drug Indication Benidipine is a potent and long-lasting drug indicated for the treatment of cardiovascular diseases such as hypertension, renoparenchymal hypertension and angina pectoris. Mechanism of Action Benidipine is a tripe calcium channel inhibitor by inhibiting L, N and T type calcium channel. It presents a very long-lasting activity that can be explained by its high affinity for cell membranes from the DHP binding site; this characteristic indicated a long-lasting pharmacological activity of benidipine. The additional property of benidipine is the vascular selectivity towards peripheral blood vessels. Pharmacodynamics Benidipine reduces systolic and diastolic blood pressure as well as to present decreases in heart rate pulse after treatment. It is reported also a decrease urinary protein excretion and serum triglycerides. Different studies have shown benidipine anti-oxidative activity, stimulation of NO production, suppression of adhesion molecules expression, stimulation of osteoblast differentiation, suppression of the proliferation of vascular smooth muscle cells and mesangial cells, as well as myocardial protection. The enhancement of NO production is associated with the cardioprotective and antiartheriosclerotic effects of benidipine. |
| Molecular Formula |
C28H31N3O6
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|---|---|
| Molecular Weight |
505.56224
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| Exact Mass |
505.221
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| CAS # |
105979-17-7
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| Related CAS # |
Benidipine hydrochloride;91599-74-5;(Rac)-Benidipine-d7
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| PubChem CID |
656668
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
625.2±55.0 °C at 760 mmHg
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| Melting Point |
>193ºC
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| Flash Point |
331.9±31.5 °C
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| Vapour Pressure |
0.0±1.8 mmHg at 25°C
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| Index of Refraction |
1.622
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| LogP |
4.92
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
37
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| Complexity |
933
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CC1=C([C@H](C(=C(N1)C)C(=O)O[C@@H]2CCCN(C2)CC3=CC=CC=C3)C4=CC(=CC=C4)[N+](=O)[O-])C(=O)OC
|
| InChi Key |
QZVNQOLPLYWLHQ-ZEQKJWHPSA-N
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| InChi Code |
InChI=1S/C28H31N3O6/c1-18-24(27(32)36-3)26(21-11-7-12-22(15-21)31(34)35)25(19(2)29-18)28(33)37-23-13-8-14-30(17-23)16-20-9-5-4-6-10-20/h4-7,9-12,15,23,26,29H,8,13-14,16-17H2,1-3H3/t23-,26-/m1/s1
|
| Chemical Name |
5-O-[(3R)-1-benzylpiperidin-3-yl] 3-O-methyl (4R)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
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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 | 1.9780 mL | 9.8900 mL | 19.7800 mL | |
| 5 mM | 0.3956 mL | 1.9780 mL | 3.9560 mL | |
| 10 mM | 0.1978 mL | 0.9890 mL | 1.9780 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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