PHARMACOLOGICAL PROFILE OF SEMOTIADIL FUMARATE, A NOVEL CALCIUM-ANTAGONIST, IN RAT EXPERIMENTAL ANGINA MODEL

1 The aim of the present study was to determine whether antianginal efficacy of semotiadil fumarate (SD-3211), a structurally novel calcium antagonist, is distinct from those of diltiazem, nifedipine and nisoldipine. 2 First, the duration of the inhibitory effects of semotiadil was compared with that of other Ca2+ antagonists in rat experimental angina evoked by vasopressin. Semotiadil (10 mg kg(-1), p.o.) was effective for at least 9 h in the anginal model and those effects of semotiadil were longer-lasting than those of diltiazem (30 mg kg(-1), p.o.), nifedipine (10 mg kg(-1), p.o.), and nisoldipine (3 mg kg(-1), p.o.). 3 Second, the selectivity of actions of these Ca2+ antagonists for the coronary arteries and myocardium was evaluated in rat isolated perfused hearts. Diltiazem (10(-6) M) reduced cardiac contractility without inhibiting the elevation of perfusion pressure evoked by acetylcholine. Semotiadil (10(-7) M) significantly suppressed cardiac contractility and inhibited the coronary response to acetylcholine. In contrast, nifedipine (3 x 10(-9)-3 x 10(-8) M) and nisoldipine (3 x 10(-10)-10(-8) M) did not reduce cardiac contractility at concentrations which significantly inhibited the increase in perfusion pressure to acetylcholine. 4 The selectivity of semotiadil for coronary artery and myocardium is intermediate between diltiazem and dihydropyridines tested in the present study. 5 These findings suggest that semotiadil has an advantage of diltiazem, nifedipine, and nisoldipine in the treatment of angina with regard to long-lasting action and selectivity for coronary artery and myocardium.