Antianginal effects of ranolazine in various experimental models of angina

The effects of ranolazine (CAS 95635-55-5, KEG-1295), a novel antianginal d rug, on the ST-segment changes induced by coronary ligation, epinephrine, a nd vasopressin were examined following oral or intraduodenal administration . In anesthetized dogs, intraduodenal administration of KEG-1295 (10, 30, o r 50 mg/kg) or atenolol(10 mg/kg) significantly attenuated the ST-T wave el evation induced by 2-min coronary ligation imposed during electrical heart pacing (200 beats/min). This antianginal effect of KEG-1295 persisted for 3 h without any changes in hemodynamic parameters, while that of atenolol wa s accompanied by more or less maintained decreases in diastolic blood press ure, heart rate, and the maximum first derivative of left ventricular press ure. In anesthetized rats, oral administration of KEG-1295 (10, 30, or 50 m g/kg) attenuated the ST-T wave elevation induced by epinephrine (0.3 mu g/k g i.v.) in a dose-dependent manner, although KEG-1295 (10 or 30 mg/kg p.o,) failed to attenuate the ST-segment depression induced by vasopressin (0.2 IU/kg i.v.). These findings suggest that, taken orally, KEG-1295 may exert potent protective effects against angina pectoris, except that caused by va sospasm. Further, KEG-1295 may be categorized as a new type of antianginal agent, without any primary hemodynamic effects.