The Sound of Evolution
Nicorandil
Mechanism of action:
Nicorandil has a dual mechanism of action, combining nitric oxide-mediated vasodilation with potassium channel opening activity. One end of the nicorandil molecule contains a nitrate ester structure that releases nitric oxide in vascular smooth muscle, activates guanylyl cyclase, increases cGMP, and causes smooth muscle relaxation and vasodilation. The other end opens ATP-sensitive potassium channels, allowing potassium efflux and inducing membrane hyperpolarization. This closes calcium channels, reduces calcium influx, and further relaxes vascular smooth muscle.
Reference(s):
1. Kukovetz WR et al. (1992). Molecular mechanism of action of nicorandil. J Cardiovasc Pharmacol.
2. Russ U et al. (2003). Binding and effect of K ATP channel openers in the absence of Mg²⁺. Br J Pharmacol.
3. Yamada M et al. (2004). The nucleotide-binding domains of sulfonylurea receptor 2A and 2B play different functional roles in nicorandil-induced activation of ATP-sensitive K+ channels. Mol Pharmacol.