Manidipine 2HCl

Alias: Manidipine HCl; CV-4093; CV4093; CV 4093
Cat No.:V1551 Purity: ≥98%
Manidipine 2HCl (alsocalled CV-4093;CV4093), the dihydrochloride saltform of Manidipine, is a calcium channel blocker/CCB that is used clinically as an antihypertensive agent.
Manidipine 2HCl Chemical Structure CAS No.: 89226-75-5
Product category: CDK
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
50mg
100mg
250mg
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1g
Other Sizes

Other Forms of Manidipine 2HCl:

  • Manidipine (CV-4093)
Official Supplier of:
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

Manidipine 2HCl (also called CV-4093; CV4093), the dihydrochloride salt form of Manidipine, is a calcium channel blocker/CCB that is used clinically as an antihypertensive agent. It inhibits the voltage-dependent calcium inward currents in smooth muscle cells, which results in systemic vasodilation. Comparing manidipine to other Ca2+ channel antagonists, it is said to exhibit minimal cardiodepression and selectively block T-type Ca2+ channels while having a high selectivity for the vasculature.

Biological Activity I Assay Protocols (From Reference)
Targets
CDK7/CycH/MAT1 (IC50 = 0.021 μM); CDK2/Cyc E (IC50 = 0.88 μM); CDK5/p35NCK (IC50 = 3 μM); CDK9/cycT (IC50 = 4.2 μM); CDK1/cycB (IC50 = 8.1 μM); CDK4/Cyc D1 (IC50 = 33 μM); CDK6/cycD1 (IC50 = 47 μM)
ln Vitro

Manidipine reduces the Ca2+ current at concentrations above 0.1 nM and eliminates it at 100 nM, with a holding potential of -37 mV. The calcium concentration response curves are inhibited by manidipine in a concentration-dependent manner [1]. Manidipine has a pIC50 of 9.3 nM for the renal artery and 9.1 nM for the coronary artery, respectively. [2] Manidipine reduces the mean arterial pressure response to norepinephrine infusion and partially inhibits sympathetic nerve activity. Moreover, manidipine prevents aldosterone secretion. Urine manidipine raises uric acid and calcium levels. [/3] Furthermore, manidipine effectively modifies gene transcriptions implicated in proinflammatory alterations in mesangial cells at nanomolar concentrations. *[4]

ln Vivo
Manidipine (3 mg/kg and 10 mg/kg, p.o.) reduces systolic blood pressure in the three types of hypertensive rats in a dose-dependent manner. Manidipine reduces blood pressure to normotensive levels at a dose of 10 mg/kg within 1 to 3 hours of administration; the antihypertensive effect lasts for at least 8 hours. [5] The hypotensive effect is significantly enhanced by 10 μg/kg of manidipine. (6) At -60 mV potential, manidipine potently inhibits the Ca inward current. The Ca current elicited by depolarization to 0 mV is consistently inhibited by manidipine. The Ca current induced by the -20 mV depolarizing pulse, however, is enhanced by a low concentration of manidipine (1-3 nM) when the membrane potential is maintained at -80 mV.
Cell Assay
The amount of [3H]thymidine incorporated into the DNA of human MCs and the evaluation of cell proliferation are used to quantify the mitogenic effect. To summarize, a 25-mL cell culture bottle is seeded with 1 × 105 quiescent cells, which are maintained in low serum medium containing 0.1% FCS. The next day, the cells are either incubated with low serum medium (abone) or stimulated with PDGF-BB (10 ng/mL) after being preincubated with manidipine (10 nM) for three hours. Every day, the medium is changed, and on days 1, 3, and 5, the cells are counted.
Animal Protocol
Normotensive male Wistar-Kyoto rats and male stroke-prone SHR
1 mg/kg, 3 mg/kg and 10 mg/kg
Administered via p.o.
References

[1]. Eur J Pharmacol . 1993 Nov 9;249(2):231-3.

[2]. TAm Heart J . 1993 Feb;125(2 Pt 2):571-7.

[3]. Am Heart J . 1993 Feb;125(2 Pt 2):635-41.

[4]. Proc Natl Acad Sci U S A . 1992 May 1;89(9):4071-5

[5]. Jpn J Pharmacol . 1988 Oct;48(2):223-8.

[6]. Jpn J Pharmacol . 1989 Oct;51(2):257-65.

[7]. J Pharmacol Exp Ther . 1987 Nov;243(2):703-10.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C35H38N4O6.2HCL
Molecular Weight
683.62
Exact Mass
682.2324904
Elemental Analysis
C, 61.49; H, 5.90; Cl, 10.37; N, 8.20; O, 14.04
CAS #
89226-75-5
Related CAS #
Manidipine;89226-50-6
Appearance
Solid powder
SMILES
CC1=C(C(C(=C(N1)C)C(=O)OCCN2CCN(CC2)C(C3=CC=CC=C3)C4=CC=CC=C4)C5=CC(=CC=C5)[N+](=O)[O-])C(=O)OC.Cl.Cl
InChi Key
JINNGBXKBDUGQT-UHFFFAOYSA-N
InChi Code
InChI=1S/C35H38N4O6.2ClH/c1-24-30(34(40)44-3)32(28-15-10-16-29(23-28)39(42)43)31(25(2)36-24)35(41)45-22-21-37-17-19-38(20-18-37)33(26-11-6-4-7-12-26)27-13-8-5-9-14-27;;/h4-16,23,32-33,36H,17-22H2,1-3H3;2*1H
Chemical Name
5-O-[2-(4-benzhydrylpiperazin-1-yl)ethyl] 3-O-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate;dihydrochloride
Synonyms
Manidipine HCl; CV-4093; CV4093; CV 4093
HS Tariff Code
2934.99.9001
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)
Solubility Data
Solubility (In Vitro)
DMSO: ~21 mg/mL (~30.7 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In Vivo)
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.66 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 25.0 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: ≥ 2.5 mg/mL (3.66 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 3: 2% DMSO +30%PEG 300 +ddH2O: 2mg/mL


 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 1.4628 mL 7.3140 mL 14.6280 mL
5 mM 0.2926 mL 1.4628 mL 2.9256 mL
10 mM 0.1463 mL 0.7314 mL 1.4628 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.

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Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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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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