Effects of Sematilide, a Novel Class III Antiarrhythmic Agent, on Action Potential in Guinea Pig Atrium

[摘要] References(22)Cited-By(5)Electrophysiological effects of sematilide, a novel class III antiarrhythmic agent, were examined and compared with those of (±)sotalol in guinea pig left atrium by a conventional microelectrode technique. Application of 0.1-1000 μM sematilide or 1-1000 μM (±)sotalol concentration-dependently prolonged the duration of action potentials (APD) that were elicited by electrical stimulation at 1 Hz. Other parameters of action potentials such as the maximum upstroke velocity of phase 0 depolarization, action potential amplitude and resting membrane potential were not affected significantly by these drugs in the concentration ranges employed. The prolongation of APD by sematilide or (±)sotalol was accompanied by a corresponding increase in the effective refractory period (ERP). Approximately a 30% increase in ERP was obtained by the treatment with 5 μM sematilide or 100 μM (± )sotalol, suggesting that sematilide as a class III antiarrhythmic agent is approximately 20 times more potent than (±)sotalol on a molecular basis. When the stimulation rate was increased stepwise from 0.2 to 2 Hz, the relative increase in APD at 90% repolarization by the treatment with sematilide and (±)sotalol was slightly larger at 2 Hz than at 0.2 Hz, indicating that “reverse rate-dependence” was not observed under these conditions. These results may suggest a possibility that sematilide effectively blocks atrial arrhythmia.

[学科分类] 药理学

[关键词] Sematilide;Antiarrhythmic agent (class III);Action potential duration;Frequency-dependence;Atrium (guinea pig)