Effects of sematilide, a novel class III antiarrhythmic agent, on action potential in guinea pig atrium.
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 microM sematilide or 1-1000 microM (+/-)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 microM sematilide or 100 microM (+/-)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.
Ishii
Y
Y
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Nagoya City University, Japan.
Muraki
K
K
Kurihara
A
A
Imaizumi
Y
Y
Watanabe
M
M
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004558:Electric Stimulation; D004594:Electrophysiology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000166:cytology; D011342:Procainamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D013015:Sotalol / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; C062818:sematilide; D013015:Sotalol; D011342:Procainamide