EFFECTS OF N-(2-HYDROXYETHYL)NICOTINAMIDE NITRATE (SG-75) ON METHACHOLINE-INDUCED ECG CHANGES IN INTACT ANESTHETIZED RATS

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The effects of a newly developed nicotinamide derivative, N-(2-hydroxyethyl)nicotinamide nitrate (SG-75, Nicorandil), were examined in an experimental model of angina pectoris, utilizing methacholine-induced ECG changes as main parameter in intact anesthetized rats. The right carotid artery was exposed and through it a special cannula was inserted to a point near the right and left coronary ostium. Such a device made it possible to inject drugs more selectively into the coronary artery. Single intra-aortic injections of 4 to 8 μg of methacholine caused a transient elevation of the ST segment and T wave of the electrocardiogram (ECG). SG-75 (3 mg/kg i.v. or 10 mg/kg p.o.) prevented these changes in the ECG, while a potent vasodilator, papaverine, failed to do so. In the isolated, donor-perfused rat heart, SG-75 (1-30 μg) injected into the coronary perfusion system caused dose-dependent vasodilation, while 0.1-0.8 μg acetylcholine as well as methacholine produced marked vasoconstriction. SG-75 (10 mg/kg) administered orally to the donor rat inhibited the coronary vasoconstriction produced by the cholinomimetic drugs, whereas papaverine (30 μg La.) failed to prevent it. The inhibitory effects of SG-75 on methacholine-induced ECG changes in intact rats seemed to be due to its spasmolytic action.
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