Electrophysiologic effects of Org 7797, a new steroidal antiarrhythmic agent: comparison with class 1a, 1b, and 1c...

The in vitro electrophysiologic effects of a new class I steroidal antiarrhythmic agent, Org 7797 (2-10 microM) were evaluated in porcine ventricular and Purkinje tissue using conventional microelectrode techniques. Org 7797-induced decreases in Vmax were both frequency- and voltage-dependent. Both the rate of onset and the time course of decay of sodium channel block were slow and similar to those obtained with the 1c drug propafenone. The kinetics of block by lignocaine (1b) were fast whereas those of disopyramide (1a) were intermediate. Rate constants (determined at 1.0 Hz) were 0.187, 0.078, and 0.074 for disopyramide, propafenone, and Org 7797, respectively, in concentrations giving approximately equivalent decreases in Vmax. Onset block with lignocaine was too fast to measure. The effective refractory period (ERP) was prolonged to a greater extent by lignocaine and disopyramide than by propafenone or Org 7797, but the increase in ERP in response to disopyramide resulted largely from prolongation of action potential duration (APD). The effects of Org 7797 on ERP relative to APD were more similar to those of propafenone. We conclude that Org 7797 is a class 1c agent.