Cardiac electrophysiologic effects of R 54718.
We studied the cellular electrophysiologic effects of a lidocaine derivative, R-54718, that has been found effective in treating arrhythmias in experimental animals and in human subjects. R-54718 depresses Vmax, action potential amplitude, and conduction and accelerates repolarization of the canine Purkinje fiber action potential, with an effective concentration range 2 or 3 orders of magnitude lower than that of most class I antiarrhythmic drugs. Its action on Vmax shows no use dependence. In blood superfusion experiments its depressant effects on conduction are more profound than those of other class I compounds and significant toxicity can be seen. R-54718 also depresses delayed afterdepolarizations, as well as the abnormal automaticity occurring at low membrane potentials. However, automaticity occurring in fully polarized Purkinje fibers is not affected. In conclusion, R 54718 is unusual in its lack of use dependent action, in its differential action on normal and abnormal automaticity, and in its potency.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004285:Dogs; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008012:Lidocaine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D010042:Ouabain / Q000494:pharmacology; D011690:Purkinje Fibers / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; D010042:Ouabain; C052070:transcainide; D008012:Lidocaine