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Electrophysiologic Effects of RS-2135, a New Antiarrhythmic Compound, on Canine Purkinje Fibers

Electrophysiologic Effects of RS-2135, a New Antiarrhythmic Compound, on Canine Purkinje Fibers

R Yorikane, T Sada, H Koike

J Cardiovasc Pharmacol. 1992 Dec;20(6):955-60.

PMID: 1282599

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
CS31041596	Flecainide Related Compound A			Price

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