Electrophysiological Properties of SD-3211, a Novel Putative Ca2+ Antagonist, in Isolated Guinea Pig and Rabbit Hearts

Miyawaki, Nobuaki; Furuta, Tatsuji; Shigei, Tatsuro; Yamauchi, Hideyasu; Iso, Tadashi

doi:10.1097/00005344-199011000-00012

Cited by 26 publications

(20 citation statements)

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“…than that of diltiazem (Miyawaki et al, 1990;1991;Nishimura et al, 1990;Takada et al, 1991b). Furthermore, semotiadil shows long-lasting antihypertensive effects in spontaneously hypertensive rats (SHR) and renal hypertensive dogs (Kageyama et al, 1991;Takada et al, 1991a;Kanda & Hashimoto, 1993).…”

Section: Introductionmentioning

confidence: 99%

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

Mori

Ishigai

Fukuzawa

et al. 1995

British J Pharmacology

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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.

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Section: Introductionmentioning

confidence: 99%

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

Mori

Ishigai

Fukuzawa

et al. 1995

British J Pharmacology

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“…This compound is a stereoisomer of semotiadil fumarate (SD-3211), a recently developed non-dihydropyridine type calcium antagonist (Miyawaki et al, 1990;Fukuchi et al, 1990;Teramoto, 1993). In vitro and in vivo experiments on rats, guinea-pigs, and dogs, showed that SD-3212 had a potent and long lasting inhibitory or protective action against ventricular tachyarrhythmias induced by chloroform, ouabain, adrenaline, coronary occlusion and reperfusion (Fukuchi et al, 1990;Miyawaki et al, 1991;Nagashima et al, 1992).…”

mentioning

confidence: 99%

Electrophysiological effects of SD‐3212, a new antiarrhythmic agent with vasodilator action, on guinea‐pig ventricular cells

Kodama

Suzuki

Maruyama

et al. 1995

British J Pharmacology

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“…The result suggested that semotiadil can be classified as a calcium antagonist (1). The view was confirmed by a recent electrophysiological study, which indicated that semotiadil inhibited unitary calcium cur rents through voltage-dependent calcium channels (2).…”

mentioning

confidence: 67%

“…, decreased the plateau of the fast action potential without affecting the maximum up stroke velocity and depressed the slow action potential induced by isoproterenol in isolated guinea pig papillary muscles (1). The result suggested that semotiadil can be classified as a calcium antagonist (1).…”

mentioning

confidence: 95%

Effects of Semotiadil (SD-3211), a Benzothiazine Calcium Antagonist, on Blood Pressure and Atrioventricular Conductivity in Anesthetized Dogs

Kageyama

Yamada

Satoh

et al. 1992

Japanese Journal of Pharmacology

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ABSTRACT-We investigated the effects of semotiadil (SD-3211), a novel calcium antagonist, on blood pressure and the atrioventricular (AV) conduction time and functional refractory period (FRP) of the AV conduction system (AV conductivity) in anesthetized open-chest dogs. The heart was electrical ly stimulated at a constant rate. In dogs with an intact nerve supply to the heart, i.v.-injections of semotiadil (0.03 to 0.3 mg/kg) produced a fall of blood pressure in a dose-dependent manner. AV con duction time and FRP were prolonged by rather higher doses (0.3 mg/kg), and second-degree AV block occurred only with the highest dose (1 mg/kg). In dogs with the nerve supply to the heart inter rupted, the vasodepressor effects and suppressant effects of semotiadil on AV conductivity were slightly enhanced. The suppressant effects on AV conductivity became marked as pacing rates were increased. These results suggest that semotiadil at appropriate doses produces a vasodepressor effect without affecting AV conductivity even in the heart deprived of nervous control, e.g., the heart with ,8-adre noceptors blocked. The frequency-dependent suppressant effect on FRP of semotiadil is also notewor thy in the treatment of reentrant supraventricular tachycardia that involves the AV node.

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Electrophysiological Properties of SD-3211, a Novel Putative Ca2+ Antagonist, in Isolated Guinea Pig and Rabbit Hearts

Cited by 26 publications

References 0 publications

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

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

Electrophysiological effects of SD‐3212, a new antiarrhythmic agent with vasodilator action, on guinea‐pig ventricular cells

Effects of Semotiadil (SD-3211), a Benzothiazine Calcium Antagonist, on Blood Pressure and Atrioventricular Conductivity in Anesthetized Dogs

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