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    Manidipine 2HCl
    Manidipine 2HCl

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    This product is for research use only, not for human use. We do not sell to patients.
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    InvivoChem Cat #: V1551
    CAS #: 89226-75-5Purity ≥98%

    Description: Manidipine 2HCl (also called CV-4093) is the dihydrochloride salt preparation of Manidipine, which is a calcium channel blocker that is used clinically as an antihypertensive agent. It causes systemic vasodilation by inhibiting the voltage-dependent calcium inward currents in smooth muscle cell. Manidipine is described to block T-type Ca2+ channels specifically and is also described to have a high selectivity for the vasculature, presenting negligible cardiodepression as compared to other Ca2+ channel antagonists. 

    References: Proc Natl Acad Sci U S A. 1992 May 1;89(9):4071-5; Eur J Pharmacol. 2008 Jun 10;587(1-3):224-30.

    Related CAS #89226-75-5 (HCl); 89226-50-6 (free base)    

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    Molecular Weight (MW)683.62
    FormulaC35H38N4O6.2HCl
    CAS No.89226-75-5
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 21 mg/mL (30.7 mM)
    Water: <1 mg/mL
    Ethanol: <1 mg/mL
    Solubility (In vivo)2% DMSO+30% PEG 300+ddH2O: 2 mg/mL
    SynonymsCV-4093; CV4093; CV 4093


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    In Vitro

    In vitro activity: At a holding potential of −37 mV, Manidipine decreases the Ca2+ current at concentrations above 0.1 nM, and abolishes it at 100 NM.  Manidipine concentration-dependently inhibits the calcium concentration response curves. Manidipine inhibits coronay artery and renal artery with pIC50 of 9.3 nM and 9.1 nM, respectively. Manidipine partly inhibits sympathetic nerve activity and suppresses the mean arterial pressure response to infused norepinephrine. Manidipine also inhibits aldosterone secretion. Manidipine increases in both urinary calcium and uric acid. In addition, Manidipine, at nanomolar concentrations, is efficacious in modulating gene transcriptions that are involved in proinflammatory changes of mesangial cells.


    Cell Assay: The mitogenic effect is measured by the amout of [3H]thymidine incorporated into DNA of human MCs and by assessment of cell proliferation. In brief, 1 × 105 quiescent cells is seeded into a 25-mL cell culture bottle and kept in low serum medium (0.1% FCS). On the following day, the cells are preincubated for 3 hours with Manidipine (10 nM) followed by stimulation with PDGF-BB (10 ng/mL) or incubated with low serum medium abone. The medium is replaced each day, and the cells are counted at days 1, 3 and 5.

    In VivoManidipine (3 mg/kg and 10 mg/kg, p.o.) dose-dependently decreases systolic blood pressure in the three types of hypertensive rats. At the dose of 10 mg/kg, Manidipine decreases the blood pressure to the normotensive level between 1 hour and 3 hours after Manidipine is administered; the antihypertensive effect lasted for at least 8 hours. When Manidipine is administered at 10 μg/kg, the hypotensive action is markedly augmented. Manidipine potently inhibits the Ca inward current, When the potential is at -60 mV. Manidipine consistently inhibits the Ca current evoked by depolarization to 0 mV. However, a low concentration of Manidipine (1-3 nM) enhances the Ca current evoked by the depolarizing pulse of -20 mV, when the membrane potential is held at -80 mV. Inhibition of the Ca current induced by Manidipine develops slowly and over 10 minutes is required to reach the maximum inhibition.
    Animal modelNormotensive male Wistar-Kyoto rats and male stroke-prone SHR 
    Formulation & DosageDissolved in saline; 1 mg/kg, 3 mg/kg and 10 mg/kg; oral administration
    References

    Proc Natl Acad Sci U S A. 1992 May 1;89(9):4071-5; Eur J Pharmacol. 2008 Jun 10;587(1-3):224-30; Eur J Pharmacol. 1993 Nov 9;249(2):231-3; Jpn J Pharmacol. 1989 Oct;51(2):257-65; J Pharmacol Exp Ther. 1987 Nov;243(2):703-10.


    These protocols are for reference only. InvivoChem does not independently validate these methods.

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