Mechanism of action of ranolazine, trimetazidine and nicorandil

Mechanism of action of ranolazine, trimetazidine and nicorandil

Conventional mainstay of anti anginal therapy are beta blockers, nitrates and calcium channel blockers. They mostly decrease myocardial oxygen demand with little effect on the myocardial oxygen supply or utilization. Even for nitrates, the predominant effect is venodilatation and reduction of preload and hence the myocardial oxygen demand rather than coronary vasodilatation and increase in supply. Hence the maximum rate pressure product achieved, the determinant of peak myocardial oxygen demand, is seldom altered.

Ranolazine inhibits the late sodium current and hence the calcium influx into the ischemic myocardium. This reduces myocardial diastolic wall tension and enhances blood flow into the ischemic myocardium, which is predominantly diastolic.

Trimetazidine inhibits beta oxidation of fatty acids partially and shifts the myocardial metabolism towards glucose which utilizes less oxygen per ATP produced.

Nicorandil on the other hand induces pharmacological preconditioning akin to ischemic preconditioning as well as produces dilatation of coronary resistance vessels.