Controlled comparison of the pharmacodynamic effects of nicorandil (SG-75) and isosorbide dinitrate in man

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Abstract
Nicorandil (SG-75) is a long acting mononitrate. A randomized, double-blind, crossover study in 10 healthy subjects has compared the haemodynamic actions of single sublingual doses of nicorandil 15, 30 and 60 mg with Isosorbide dinitrate (ISDN) 5 mg and placebo. Heart rate, blood pressure, systolic time intervals (STI) and left ventricular echocardiograms were used to assess haemodynamics over a 6 h period. Within 15 min of nicorandil administration, heart rate increased and peripheral resistance decreased (dose-dependent); the preejection period (corrected; PEPc) and the ratio of PEP to left ventricular ejection time (LVET) — PEP/LVET — were shortened by the 60 mg dose; the heart rate corrected electromechanical systole (QS2c) was almost unchanged; left ventricular end diastolic and systolic diameters (EDD and ESD) were diminished. The effects on certain parameters had not completely disappeared after 6 h. ISDN produced a similar pattern with somewhat less intense effects; although PEPc and PEP/LVET were prolonged. The effects of both drugs can be attributed to vasodilatation on both the arteriolar and venous sides. The predominant action of ISDN was to reduce preload and thereby to lengthen PEPc and PEP/LVET; in addition, it lessened afterload. Although nicorandil caused a distinct reduction in preload, as shown by the smaller EDD, the effects of afterload reduction were predominant at the high dose induced shortening of PEPc and PEP/LVET. The profile of action of nicorandil should encourage clinical testing to evaluate its ability to induce ventricular unloading.