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

Abstract

1 The aim of the present study was to determine whether antianginal efficacy of semotiadil fumarate (SD-321 1), 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 Ca2l antagonists in rat experimental angina evoked by vasopressin. Semotiadil (10 mg kg-', 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', p.o.), nifedipine (10 mg kg-', p.o.), and nisoldipine (3 mg kg-', p.o.).3 Second, the selectivity of actions of these Ca2l antagonists for the coronary arteries and myocardium was evaluated in rat isolated perfused hearts. Diltiazem (10 M) reduced cardiac contractility without inhibiting the elevation of perfusion pressure evoked by acetylcholine. Semotiadil (10-M) significantly suppressed cardiac contractility and inhibited the coronary response to acetylcholine. In contrast, nifedipine (3 x 0 9-3 x 108 M) and nisoldipine (3 x I&0°-14I 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.

Combined Effects of Benidipine and Diltiazem in a Rat Model of Experimental Angina

“…Changes in ST-segment were used as an index of ischemic severity. According to the previous report (2), the fall of S-wave was regarded as the fall of ST. Maximal S-wave depression was observed 4 -5 min following AVP injection, consistent with previous reports (10,11). Both benidipine (3 and 10 m g / kg) and diltiazem (300 and 1000 mg/ kg) significantly inhibited the S-wave depression in a dose-dependent manner (Fig.…”

Antiischemic Properties of Fasudil in Experimental Models of Vasospastic Angina

“…Additional research is required to determine the optimal dosage and timing of administration of fasudil to obtain its maximum efficacy. ECG changes induced by vasopressin indicated a subendocardiac ischemia (17). Vasopressin is considered to be a vasoconstrictor of the coronary artery (18).…”

Effects of Benidipine in a Rat Model of Experimental Angina

“…According to a previous report, 5) the fall of the Swave was regarded as the fall of ST. Maximal S-wave depression was observed about 4 min after AVP injection (data not shown), and is consistent with the results of previous reports. [7][8][9] Benidipine signiˆcant-ly inhibited the depression at 3 and 10 mg/kg in a dose-dependent manner (Fig. 2).…”

“…4) AVP-induced angina is a useful model for evaluating the e‹cacy of compounds in vasospastic angina. [5][6][7][8] Karasawa et al 5) reported that benidipine has beneˆ-cial eŠects in various experimental angina models, including the AVP-induced angina model. We have demonstrated recently that the antianginal e‹cacy of benidipine 10 mg/kg was similar to that of diltiazem 1000 mg/kg in the AVP-induced angina rat model, indicating that benidipine exerts potent antivasospastic anginal eŠects.…”