Sematilide has direct negative chronotropic and positive inotropic effects and prolongs cardiac refractoriness without affecting conduction velocities, with potency similar to MS-551.
Does sematilide prolong cardiac refractoriness and exert chronotropic and inotropic effects compared to E-4031 and MS-551 in canine heart models?
Sematilide demonstrates direct negative chronotropic and positive inotropic effects and prolongs cardiac refractoriness in a reverse frequency-dependent manner, with a potency similar to MS-551 but lower than E-4031.
Direct cardiac effects of sematilide, a new class III antiarrhythmic drug, were compared with those of E-4031 and MS-551 in canine isolated blood-perfused heart preparations. Doses of sematilide, E-4031, and MS-551 causing a 10% decrease in the spontaneous sinoatrial beating rate were 58 +/- 15, 9 +/- 5, and 84 +/- 10 micrograms (n = 5); those causing a 10% increase in developed tension of the papillary muscle were 485 +/- 49, 17 +/- 2, and 267 +/- 50 micrograms (n = 6); and those causing a 10% prolongation of effective refractory period (ERP) of the atrioventricular node were 68 +/- 10, 11 +/- 2, and 53 +/- 15 micrograms (n = 5), respectively. There were few effects on atrio-His or His-ventricular intervals. Also, in in situ open-chest dog hearts, the percent increases in ERP of the atrioventricular conduction system caused by 1 mg/kg of sematilide were 21 +/- 3, 16 +/- 2 and 9 +/- 1% at cycle lengths of 800, 600, and 400 ms, respectively (p < 0.01; n = 8). These results indicate that (a) sematilide, as well as E-4031 and MS-551, has direct negative chronotropic and positive inotropic effects and prolongs cardiac refractoriness without affecting conduction velocities; (b) quantitatively, the cardiac effects of sematilide were almost identical to those of MS-551 and five to ten times less potent than those of E-4031; (c) and prolongation of ERP of the atrioventricular conduction system by sematilide occurred in a reverse frequency-dependent manner.
Yamada et al. (Mon,) reported a other. Sematilide vs. E-4031 and MS-551 was evaluated on Direct negative chronotropic and positive inotropic effects, and prolongation of effective refractory period (ERP). Sematilide has direct negative chronotropic and positive inotropic effects and prolongs cardiac refractoriness without affecting conduction velocities, with potency similar to MS-551.