Manidipine-d4 (Synonyms: Franidipine-d4, (±)-Manidipine-d4)

Manidipine-d₄ is intended for use as an internal standard for the quantification of manidipine by GC- or LC-MS. Manidipine is a dihydropyridine L- and T-type calcium channel blocker.^1,2,3 It inhibits recombinant rabbit L-type (α_1Cα₂/δβ_1a) and human T-type (α_1H) calcium channels expressed in Xenopus oocytes and native L-type channels in dissociated guinea pig cardiac ventricular cells (IC₅₀ = 2.6 nM). Manidipine inhibits intracellular calcium increases induced by endothelin-1 in A₇r₅ rat vascular smooth muscle cells (ED₅₀ = 1 nM) and potassium-induced contraction of isolated dog femoral and portal veins (IC₅₀s = 24 and 2.1 nM, respectively).^4,5 In vivo, it lowers blood pressure in spontaneously hypertensive rats (SHRs) when administered at a dose of 10 mg/kg and inhibits left ventricular hypertrophy in rats induced by isoproterenol when administered at a dose of 3 mg/kg.^6,7 Formulations containing manidipine have been used in the treatment of hypertension.

1.Furukawa, T., Nukada, T., Miura, R., et al.Differential blocking action of dihydropyridine Ca2+ antagonists on a T-type Ca2+ channel (α1G) expressed in Xenopus oocytesJ. Cardiovasc. Pharmacol.45(3)241-246(2005) 2.Furukawa, T., Nukada, T., Namiki, Y., et al.Five different profiles of dihydropyridines in blocking T-type Ca2+ channel subtypes (Cav3.1 (α1G), Cav3.2 (α1H), and Cav3.3 (α1I)) expressed in Xenopus oocytesEur. J. Pharmacol.613(1-3)100-107(2009) 3.Tohse, N., Takeda, Y., and Kanno, M.Voltage-dependent modulation of L-type Ca2+ current by manidipine in guinea-pig heart cellsEur. J. Pharmacol.249(2)231-233(1993) 4.Huang, S., Simonson, M.S., and Dunn, M.J.Manidipine inhibits endothelin-1-induced [Ca2+]i signaling but potentiates endothelin's effect on c-fos and c-jun induction in vascular smooth muscle and glomerular mesangial cellsAm. Heart J.125(2 Pt 2)589-597(1993) 5.Shibouta, Y., Kitayoshi, T., Kitoh, G., et al.Calcium channel blocking action of franidipine hydrochloride (CV-4093.2HCl) in vitro and in vivoJpn. J. Pharmacol.48(4)463-472(1988) 6.Meguro, K., Aizawa, M., Sohda, T., et al.New 1,4-dihydropyridine derivatives with potent and long-lasting hypotensive effectChem. Pharm. Bull. (Tokyo)33(9)3787-3797(1985) 7.Yoshiyama, M., Takeuchi, K., Kim, S., et al.Effect of manidipine hydrochloride, a calcium antagonist, on isoproterenol-induced left ventricular hypertrophyJpn. Circ. J.62(1)47-52(1998)