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Manidipine dihydrochloride (CV-4093) is a hydrochloride salt of manidipine that is a lipophilic, third-generation, highly vasoselective dihydropyridine calcium antagonist with an IC50 of 2.6 nM. Manidipine dihydrochloride (CV-4093) causes systemic vasodilation by inhibiting the voltage-dependent calcium inward currents in smooth muscle cells. Manidipine dihydrochloride (CV-4093) is used clinically as an antihypertensive. Manidipine dihydrochloride (CV-4093) suppressed the DNA synthesis of vascular smooth muscle cells (VSMC) dose dependently at concentrations of more than 10 nM. Mandipine hydrochloride (1 uM) suppressed proliferation of VSMC to 50% of the control value. Manidipine hydrochloride stimulated the synthesis of GAG at concentrations above 0.01 nM. Manidipine hydrochloride (10 nM) stimulated synthesis of glycosaminoglycans (GAG) to 450% of control.
| Cell Experiment | |
|---|---|
| Cell lines | Mesangial cells |
| Preparation method | Measuring the mitogenic effect by the amout of [3H]thymidine incorporated into DNA of human MCs and by assessment of cell proliferation. In brief, seeding 1 ?105 quiescent cells into a 25-mL cell culture bottle and keeping in low serum medium (0.1% FCS). On the next 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. Replacing the medium each day, and counting the cells at days 1, 3 and 5. |
| Concentrations | 10 nM |
| Incubation time | Days 1, 3 and 5 |
| Animal Experiment | |
|---|---|
| Animal models | Normotensive male Wistar-Kyoto rats and male stroke-prone SHR |
| Formulation | Saline |
| Dosages | 1 mg/kg, 3 mg/kg and 10 mg/kg |
| Administration | Administered via p.o. |
| Molecular Weight | 683.62 |
| Formula | C35H38N4O6.2HCl |
| CAS Number | 89226-75-5 |
| Solubility (25°C) | DMSO 20 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
[1] Luca Cavalieri, et al. Metabolic effects of manidipine
[2] Paul L McCormack, et al. Delapril/manidipine
[3] Alex Roca-Cusachs, et al. Antihypertensive effect of manidipine
[4] Kate McKeage, et al. Manidipine: a review of its use in the management of hypertension
[5] S M Cheer, et al. Manidipine: a review of its use in hypertension
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