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

Abstract

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+]j. 5 Higher concentrations of lignocaine (8 to 16 mg/i) did, however, reduce MRD at both [K+].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 I antidysrhythmic drugs.

Prophylactic Lignocaine and Early Post‐coronary Artery Occlusion Dysrhythmias in Anaesthetized Greyhounds

“…Studies on human ventricular muscle (Kane, 1980) have shown that lignocaine differs from Org 6001 (and quinidine) in its actions on absolute refractory period. However until the genesis of ventricular fibrillation is better understood, the relevance of these subtle differences in the electrophysiological profile of Class I antiarrhythmic drugs remains unclear.…”

Maturing human pluripotent stem cell-derived cardiomyocytes in human engineered cardiac tissues

“…Lidocaine treatment prolonged the APD and slowed Vmax in human ventricular muscle preparations [232]. In hiPSC-CMs, lidocaine blocked Na + influx and decreased conduction velocity but did not affect the APD [233].…”

Voltage‐ and Time‐dependent Depression of Maximum Rate of Depolarization of Guinea‐pig Ventricular Action Potentials by Two Steroidal Antiarrhythmic Drugs, Cci 22277 and Org 6001

“…Vaughan Williams & Wittig, 1976;Kane, 1980). CCI 22277 was developed more recently and shown to be more potent than Org 6001 at suppressing aconitine- CH3 ,CH ( () The Macmillan Press Ltd 1982 induced arrhythmias in the rat (Dodds, Dolamore, Sawyer, Straughan & Twissel, 1982).…”