Paper
Cellular Electrophysiological Effects of the Class III Antiarrhythmic Agents Sematilide and Clofilium on Rabbit Atrial Tissues
Published Jul 1, 1991 · T. Argentieri, M. S. Carroll, M. Sullivan
Journal of Cardiovascular Pharmacology
27
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Abstract
Sematilide (N-[2-(diethylamino)ethyl]-4-[(methylsulfonyl)amino]benzamide HCl) is a new class III antiarrhythmic agent that has been shown to be effective in preventing reentrant ventricular arrhythmias in experimental animals and humans. In this study, we examined the in vitro effects of sematilide (1–100 μM) on isolated sinoatrial (SA) node, atrioventricular (AV) node, and atrial muscle. These results were then compared to another class III agent, clofilium (1–30 μM). In SA nodal tissue, sematilide increased the action potential duration (APD) and spontaneous cycle length (SCL) in a concentration-dependent manner (EC20 = 15 ± 3 and 54 ± 13 μM, respectively). In addition, there was a slight reduction in maximum diastolic potential at 100 μM. Clofilium had similar class III effects, but was approximately 3 to 18 times more potent (EC20 = 6 ± 2 and 3 ± 1 μM for the APD and SCL, respectively). Neither agent had a significant effect on the slope of phase 4 nor on other action potential parameters. Results in AV nodal preparations were similar. Both sematilide and clofilium increased the APD and SCL in a concentration-dependent manner, with clofilium being approximately four to six times more potent than sematilide (EC20 for the APD and SCL for sematilide = 12 ± 4 and 12 ± 8 μM, respectively, and for clofilium = 2 ± 1 and 3 ± 2 μM, respectively). No significant effects were observed on other action potential parameters. Sematilide and clofilium increased the APD and effective refractory period (ERP) in atrial trabeculae in a concentration-dependent manner. Consistent with the other preparations, clofilium was approximately three to seven times more potent than sematilide (EC20 for the APD and ERP for sematilide = 34 ± 10 and 14 ± 3 μM, respectively, and for clofilium = 10 ± 4 and 2 ± 1 μM. respectively). At 30 μM, clofilium also decreased the action potential amplitude and maximum upstroke velocity (Vmax). The membrane responsiveness data suggest that clofilium produces mainly tonic inhibition of the sodium channel. In summary, sematilide and clofilium have significant class III effects in atrial tissues that might be useful in the treatment of reentrant atrial arrhythmias.
In Vitro StudySematilide and clofilium both have significant class III effects in atrial tissues, potentially useful in treating reentrant atrial arrhythmias.
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