COMPARATIVE ELECTROPHYSIOLOGICAL EFFECTS OF Org 6001, A NEW ORALLY ACTIVE ANTIDYSRHYTHMIC AGENT, AND LIGNOCAINE ON HUMAN VENTRICULAR MUSCLE

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Abstract
1 The electrophysiological effects of Org 6001, a new orally active antidysrhythmic agent, have been compared with those of lignocaine on the human ventricular action potential in vitro.2 Org 6001 (4 to 16 mg/l) greatly reduced the maximum rate of depolarization (MRD) of the human ventricular action potential but had no effect on resting membrane potential or action potential amplitude.3 The action potential duration at the 50% repolarization level, but not at the 90% repolarization level, was significantly reduced by Org 6001. The absolute refractory period was unchanged.4 Lignocaine, at a concentration (4 mg/l) within the therapeutic range, had no significant effect on any measured parameter, either in muscle exposed to a normal (4.0 mM) or high (5.4 mM) extracellular potassium concentration ([K(+)](o)).5 Higher concentrations of lignocaine (8 to 16 mg/l) did, however, reduce MRD at both [K(+)](o) without changing resting membrane potential or action potential amplitude. The action potential duration was decreased slightly by these higher concentrations of lignocaine whilst the absolute refractory period was lengthened.6 Org 6001 was found to be more potent than lignocaine in reducing MRD but, unlike lignocaine, the absolute refractory period was not prolonged. These compounds, therefore, differed in their electrophysiological effects on human ventricular muscle although both are characterized as being class 1 antidysrhythmic drugs.