Pharmacological profile of semotiadil fumarate, a novel calcium antagonist, in rat experimental angina model

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Abstract
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.