Nicorandil-d4

Nicorandil-d₄ is intended for use as an internal standard for the quantification of nicorandil by GC- or LC-MS. Nicorandil is an activator of sulfonylurea receptor 2B (SUR2B) linked to ATP-sensitive potassium channel K_ir6.2 (EC₅₀ = ~10 µM) and a nitric oxide (NO) donor.^1,2 It is selective for SUR2B/K_ir6.2 over the SUR2A/K_ir6.2 channel (EC₅₀ = >500 µM).¹ Nicorandil activates soluble guanylate cyclase in a cell-free assay and relaxes partially depolarized isolated bovine coronary artery strips (EC₅₀ = 4.4 µM).³ It decreases mean blood pressure, coronary resistance, and heart rate, as well as increases coronary sinus outflow, in dogs when administered intravenously at a dose of 1 mg/kg.⁴ Nicorandil increases survival and decreases infarct size in a rabbit model of myocardial ischemia-reperfusion injury induced by left coronary artery occlusion.⁵ Formulations containing nicorandil have been used in the treatment of angina pectoris.

1.Shindo, T., Yamada, M., Isomoto, S., et al.SUR2 subtype (A and B)-dependent differential activation of the cloned ATP-sensitive K+ channels by pinacidil and nicorandilBr. J. Pharmacol.124(5)985-991(1998) 2.Frampton, J., Buckley, M.M., and Fitton, A.Nicorandil. A review of its pharmacology and therapeutic efficacy in angina pectorisDrugs44(4)625-655(1992) 3.Holzmann, S.Cyclic GMP as possible mediator of coronary arterial relaxation by nicorandil (SG-75)J. Cardiovasc. Pharmacol.5(3)364-370(1983) 4.Taira, N., Satoh, K., Yanagisawa, T., et al.Pharmacological profile of a new coronary vasodilator drug, 2-nicotinamidoethyl nitrate (SG-75)Clin. Exp. Pharmacol. Physiol.6(3)301-316(1979) 5.Das, B.C., Sarkar, C., and Karanth, S.K.Effects of administration of nicorandil or bimakalim prior to and during ischemia or reperfusion on survival rate, ischemia/reperfusion-induced arrhythmias and infarct size in anesthetized rabbitsNaunyn-Schmiedeberg’s Arch. Pharmacol.364(5)383-396(2001)