USE-DEPENDENT BLOCK AND RECOVERY OF NA^+ CHANNELS BY CLASS IC ANTIARRHYTHMIC DRUGS (FLECAINIDE AND ETHACIZIN) IN CANINE VENTRICULAR MUSCLE

概要

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Electrophysiological effects of flecainide and ethacizin (class Ic antiarrhythmic drugs) were examined using conventional microelectrode techniques. Flecainide significantly depressed the maximum rate of depolarization (V^^•_max) at 3x10^<-6> M, anddepolarized the resting potential (RP) at 10^<-5> M, in a concentration-dependent manner. Ethacizin depressed V^^•_max at 10^<-6> M, and depolarized RP at 10^<-5> M, significantly. However, both drugs did not affect the effective refractory period (ERP) nor the action potential duration (75% repolarization, APD_75). Both also had no effect on the action potential amplitude (APA). On the other hand, the drugs caused a use (or rate)-dependent block of V^^•_max, and their time constants of onset of inhibition (at 3 Hz) were slow ; 6.3±1.2　msec (n=10) in the presence of flecainide (10^<-5> M), and 6.0±1.6 msec (n=6) in the presence of ethacizin (10^<-5> M). The time constants of the recovery were also so late : 12.2±2.5 sec (n=3) for flecainide (10^<-5> M), and 27.1±13.3 sec (n=3) for ethacizin (2x10^<-6> M). These results indicate that both antiarrhythmic drugs, flecainide and ethacizin, have no effect on APD_75 and ERP, but possess the characteristics for very slow kinetics of the use-dependent block and the recovery for fast Na^+ channels of cardiac muscles. Ethacizin produces slower kinetics for the Na^+ channels than flecainide.
奈良医学会の論文
1993-02-28