Electrophysiologic effects of RS-2135, a new antiarrhythmic compound, on canine Purkinje fibers.
RS-2135 is the (+) isomer of a novel, fused carbazol derivative. The agent, when administered orally, shows long-lasting antiarrhythmic effects in several models of arrhythmia. We used standard microelectrode techniques to characterize the electrophysiological effects of the agent on canine Purkinje fibers. RS-2135 reduced the maximum upstroke velocity of the action potential (Vmax) and shortened the action potential duration (APD) in a concentration-related manner (0.3-3 microM). RS-2135 decreased Vmax at lower concentrations than disopyramide, flecainide, and mexiletine. RS-2135 shortened the effective refractory period (ERP), but significantly increased the ratio of ERP to APD90. Additionally, the effects of the (-) optical isomer of RS-2135 were compared with those of RS-2135, the (+) enantiomer. The (-) isomer was much less potent than RS-2135 in decreasing Vmax. These data suggest that RS-2135 belongs to the class I or "local anesthetic" type of antiarrhythmic agent and that the stereochemistry of the drug molecule is an important determinant of Na channel blocking activity.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology*; D004206:Disopyramide / Q000494:pharmacology; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D011690:Purkinje Fibers / Q000187:drug effects*; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D015222:Sodium Channels / Q000187:drug effects; D013237:Stereoisomerism
D000889:Anti-Arrhythmia Agents; D002227:Carbazoles; D007546:Isoquinolines; D015222:Sodium Channels; C073517:RS 2135; D004206:Disopyramide