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.