Ranolazine 2HCl

Ranolazine selectively inhibits late I(Na), reduces [Na(+)](i)-dependent calcium overload and attenuates the abnormalities of ventricular repolarisation and contractility that are associated with ischaemia/reperfusion and heart failure in myocardial cells. ^[1] Ranolazine significantly and reversibly shortens the action potential duration (APD) of myocytes stimulated at either 0.5 Hz or 0.25 Hz in a concentration-dependent manner in left ventricular myocytes of dogs. Ranolazine at 5 and 10 mM reversibly shortens the duration of twitch contractions (TC) and abolished the after contraction. Ranolazine is found to bind more tightly to the inactivated state than the resting state of the sodium channel underlying I(NaL). ^[2]

Ranolazine (10 mM) significantly increases glucose oxidation 1.5-fold to 3-fold under conditions in which the contribution of glucoseto overall ATP production is low (low Ca, high FA, with insulin), high (high Ca, low Fa, with pacing), or intermediate in working hearts. Ranolazine similarly increases glucose oxidation in normoxic Langendorff hearts (high Ca, low FA; 15 mL/min). Ranolazine also significantly increases it during flow reduction to 7 mL/min, 3 mL/min, and 0.5 mL/min. Ranolazine significantly improves functional outcome, which is associated with significant increases in glucoseoxidation, a reversal of the increased FA oxidation seen in control reperfusions (versus preischemic), and a smaller but significant increase in glycolysis in reperfuse dischemic working hearts. ^[3]