| Size | Price | Stock | Qty |
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| 100mg |
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| 250mg |
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| 500mg |
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| 1g |
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| Other Sizes |
Purity: ≥98%
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.
| 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)
Manidipine 2HCl targets L-type voltage-dependent calcium channels (VDCC) on vascular smooth muscle cell membranes; the IC50 value for L-type calcium channels in rat aortic smooth muscle is 0.32 μM [7] Manidipine 2HCl has an IC50 value of 2.8 μM for myocardial L-type calcium channels, with higher selectivity for vascular calcium channels than myocardium (selectivity index=8.75) [6] |
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| ln Vitro |
Manidipine reduces the Ca 2+ 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]
Manidipine 2HCl concentration-dependently inhibits calcium influx-induced contraction of isolated rat aortic strips: the inhibition rate is 78% at 1 μM and 92% at 10 μM, with no significant effect on norepinephrine-induced contraction (indicating specific calcium channel blockage) [1] Manidipine 2HCl can dilate isolated rabbit basilar arteries: the vasodilation rate is 35% at 0.1 μM, 68% at 1 μM, and 85% at 5 μM, and the dilation effect is independent of endothelial function [5] Manidipine 2HCl inhibits calcium influx in cultured rat vascular smooth muscle cells (VSMC): it reduces 45Ca²⁺ influx by 62% at 0.5 μM, with no significant inhibitory effect on cell proliferation (cell survival rate ≥90% when concentration ≤10 μM) [6] |
| 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.
Manidipine 2HCl administered orally at a dose of 1 mg/kg significantly reduces systolic blood pressure (SBP) and diastolic blood pressure (DBP) in spontaneously hypertensive rats (SHR): 4 hours after administration, SBP decreases from 185 mmHg to 152 mmHg, DBP decreases from 132 mmHg to 105 mmHg, and the antihypertensive effect lasts for 24 hours [3] Intravenous administration of Manidipine 2HCl (0.3 mg/kg) exerts a rapid antihypertensive effect in anesthetized dogs: SBP decreases by 28 mmHg and DBP by 22 mmHg within 5 minutes, with the effect lasting more than 6 hours [2] Manidipine 2HCl administered orally at 0.5 mg/kg once daily for 4 weeks significantly lowers blood pressure in SHR without causing reflex tachycardia (heart rate change ≤±5%) [4] Oral administration of Manidipine 2HCl (1 mg/kg) has no significant effect on blood pressure in normotensive rats (SBP change ≤10 mmHg), showing a certain blood pressure-dependent antihypertensive characteristic [5] |
| Enzyme Assay |
Vascular smooth muscle cell membrane fragments (enriched in L-type calcium channels) were prepared from rat aorta. Gradient concentrations of Manidipine 2HCl were incubated with membrane suspension and radioactive isotope 45Ca²⁺ at 37°C for 30 minutes. Unbound 45Ca²⁺ was separated by filtration, and the radioactivity intensity bound to the cell membrane was detected to calculate the calcium influx inhibition rate and IC50 value [7]
Patch-clamp technique was used to record L-type calcium channel currents in cardiomyocytes: Manidipine 2HCl was serially diluted and added to the cell perfusion solution. Calcium channel currents (ICa,L) were recorded in the whole-cell patch-clamp mode, and the inhibitory effect of different concentrations of the drug on the current peak was analyzed to obtain the IC50 value by curve fitting [6] |
| 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 × 10 5 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.
Rat vascular smooth muscle cells (VSMC) were seeded in 24-well plates (1×10⁵ cells/well) and cultured for 48 hours, then incubated in calcium-free medium for 1 hour. Gradient concentrations of Manidipine 2HCl were added for pre-incubation for 30 minutes, followed by incubation with calcium-containing medium containing 45Ca²⁺ for 15 minutes; the medium was aspirated, cells were washed, and the radioactivity intensity in the cells was detected with a scintillation counter to calculate the calcium influx inhibition rate [6] Isolated rat aortic strips were prepared and suspended in a bath containing Krebs-Henseleit solution (37°C, gassed with 95% O₂+5% CO₂), equilibrated for 1 hour, then high-potassium solution (60 mM KCl) was added to induce calcium-dependent contraction; after the contraction stabilized, Manidipine 2HCl (0.01-10 μM) was added cumulatively, and the tension change of the aortic strips was recorded to calculate the dilation rate [1] |
| 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. Spontaneously hypertensive rats (SHR, 12-14 weeks old, male) were randomly divided into groups: the control group was given normal saline, and the administration groups were given Manidipine 2HCl (0.5, 1, 2 mg/kg). The drug was dissolved in 0.5% sodium carboxymethylcellulose solution and administered orally once daily for 4 weeks; tail artery blood pressure and heart rate were measured twice a week, and serum electrolyte levels were detected at the end of the experiment [4] Anesthetized dogs (weight 10-12 kg) were anesthetized with sodium pentobarbital intravenously, intubated and connected to a ventilator, and a carotid artery cannula was inserted to record blood pressure and heart rate; Manidipine 2HCl was dissolved in normal saline and injected intravenously at doses of 0.1, 0.3, and 1 mg/kg sequentially, with an interval of 30 minutes between each administration, and blood pressure and heart rate changes at different time points after administration were recorded [2] Normotensive rats and SHR (8 weeks old) were divided into two groups: the administration group was given oral Manidipine 2HCl 1 mg/kg, and the control group was given an equal volume of solvent; tail artery blood pressure was measured at 1, 4, 8, 12, and 24 hours after administration to compare the difference in blood pressure changes between the two groups [5] |
| ADME/Pharmacokinetics |
After oral administration of 1 mg/kg manidipine 2HCl to rats, the drug was rapidly absorbed, with a peak time (Tmax) of 1.5 hours, a peak plasma concentration (Cmax) of 86 ng/mL, and an oral bioavailability of 32% [4]. Manidipine 2HCl is widely distributed in rats, with the highest drug concentrations in the liver and kidneys (5.8 times and 3.2 times the plasma concentration, respectively), and lower drug concentrations in brain tissue (0.4 times the plasma concentration) [6]. Manidipine 2HCl is mainly metabolized in the liver, with an elimination half-life (t1/2) of 8.3 hours in rats; 65% of the total excretion is in feces, and 23% is in urine [4].
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| Toxicity/Toxicokinetics |
The median lethal dose (LD50) of manidipine 2HCl administered orally to mice was 1280 mg/kg, and to rats it was 1560 mg/kg, indicating that its acute toxicity was low [5]. When rats were administered 10 mg/kg manidipine 2HCl orally (once daily for 90 days), no obvious toxic symptoms were observed, weight gain was normal, and there were no statistically significant differences in liver and kidney function (ALT, AST, BUN, Cr) and blood routine indicators compared with the control group [6]. The plasma protein binding rate of manidipine 2HCl in humans was 95% ± 2% [7]. High-dose manidipine 2HCl (5 mg/kg, intravenous injection) had no significant inhibitory effect on myocardial contractility in anesthetized dogs (left ventricular ejection fraction change ≤ ± 8%) [2].
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| References | |
| Additional Infomation |
Manidipine dihydrochloride is a diarylmethane compound. Manidipine hydrochloride is a dihydropyridine calcium channel blocker that exerts its hypotensive effect by specifically blocking L-type calcium channels in vascular smooth muscle, reducing calcium ion influx, and dilating peripheral and coronary arteries [1]. Manidipine hydrochloride has higher selectivity for vascular calcium channels than myocardial calcium channels, and its inhibitory effect on the heart is mild during the hypotensive process, with good safety [3]. Manidipine hydrochloride has been approved for the treatment of essential hypertension, especially for hypertensive patients with coronary heart disease [4]. When manidipine hydrochloride is used in combination with angiotensin-converting enzyme inhibitors (ACEIs), its hypotensive effect can be synergistically enhanced without increasing the incidence of adverse reactions [2].
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| Molecular Formula |
C35H38N4O6.2HCL
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| Molecular Weight |
683.62
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| Exact Mass |
682.2324904
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| Elemental Analysis |
C, 61.49; H, 5.90; Cl, 10.37; N, 8.20; O, 14.04
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| CAS # |
89226-75-5
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| Related CAS # |
Manidipine;89226-50-6
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| PubChem CID |
150762
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| Appearance |
White to off-white solid powder
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| Boiling Point |
722ºC at 760 mmHg
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| Melting Point |
211 °C(dec.)
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| LogP |
6.482
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
47
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| Complexity |
1090
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl.O=C(C1C(C2C=C([N+](=O)[O-])C=CC=2)C(C(OCCN2CCN(C(C3C=CC=CC=3)C3C=CC=CC=3)CC2)=O)=C(C)NC=1C)OC
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| InChi Key |
JINNGBXKBDUGQT-UHFFFAOYSA-N
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| 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
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| 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
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| Synonyms |
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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. |
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| 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) |
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| 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. View More
Solubility in Formulation 3: 2% DMSO +30%PEG 300 +ddH2O: 2mg/mL |
| 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.
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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