Manidipine dihydrochloride

Manidipine dihydrochloride (CV-4093) is a dihydropyridine compound and a calcium channel blocker for Ca2+ current with IC50 of 2.6 nM. IC50 value: 2.6 nM Target: calcium channel Manidipine dihydrochloride 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. Manidipine is also described to not significantly affect norepinephrine levels, suggesting a lack of sympathetic activation with this compound. Manidipine reduces pro-inflammatory cytokines secretion in human endothelial cells and macrophages. Manidipine, unlike other third-generation dihydropyridine derived drugs, blocks T-type calcium channels present in the efferent glomerular arterioles, reducing intraglomerular pressure and microalbuminuria.

Product information

CAS Number: 89226-75-5

Molecular Weight: 683.62

Formula: C35H40Cl2N4O6

Synonym:

CV-4093

CV 4093

CV4093

Manidipine HCl

Related CAS Number:

89226-50-6 (Manidipine free base)

Chemical Name: 3-{2-[4-(diphenylmethyl)piperazin-1-yl]ethyl} 5-methyl 2, 6-dimethyl-4-(3-nitrophenyl)-1, 4-dihydropyridine-3, 5-dicarboxylate dihydrochloride

Smiles: Cl.Cl.COC(=O)C1C(C(C(=O)OCCN2CCN(CC2)C(C2C=CC=CC=2)C2C=CC=CC=2)=C(C)NC=1C)C1=CC(=CC=C1)[N+]([O-])=O

InChiKey: JINNGBXKBDUGQT-UHFFFAOYSA-N

InChi: 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

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO: 21 mg/mL(30.71 mM). Water: Insoluble.

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

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.

In Vivo:

Manidipine (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.

References:

1. Iimura O, et al. Am Heart J, 1993, 125(2 Pt 2), 635-641.
2. Pfaffendorf M, et al. Am Heart J, 1993, 125(2 Pt 2), 571-577.
3. Tohse N, et al. Eur J Pharmacol, 1993, 249(2), 231-233.

Products are for research use only. Not for human use.