Effect of KRN2391, a novel vasodilator, on various experimental anginal models in rats.

The antianginal effect of KRN2391, N-cyano-N'-(2-nitroxyethyl)-3-pyridinecarboximidamide monomethanesulfonate, on various anginal models in rats was compared with those of nifedipine and nicorandil. Angina pectoris was induced by methacholine or isoproterenol, and the change in the ST-segments in the electrocardiogram (ECG) was used as the parameter to indicate angina pectoris. The intracoronary administration of methacholine (3 micrograms) produced an elevation in the ST-segment of the ECG. This ST-elevation was inhibited by the intravenous administration of KRN2391 (30 and 100 micrograms/kg), nifedipine (100 and 300 micrograms/kg) and nicorandil (1000 and 3000 micrograms/kg). The administration of isoproterenol (10 micrograms/kg/min, i.v.) produced a depression of the ST-segment of the ECG. The intravenous administration of KRN2391 (100 micrograms/kg), nifedipine (100 micrograms/kg) and nicorandil (3000 micrograms/kg) inhibited the ECG changes induced by isoproterenol. These results suggest that KRN2391 exerts a potent protective effect on angina pectoris models compared with nifedipine and nicorandil. KRN2391 appears to be useful as an antianginal drug.