Tomohiro Mori, Y. Ishigai, A. Fukuzawa
Sep 1, 1995
Citations
0
Influential Citations
25
Citations
Quality indicators
Journal
British Journal of Pharmacology
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 × 10−9‐3times 10−8 M) and nisoldipine (3 × 10−10‐10−08 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.