An electrophysiological comparison of a novel class Ic antiarrhythmic agent, NIK-244 (ethacizin) and flecainide in canine ventricular muscle.
1. Electrophysiological effects of NIK-244 (ethacizin), a novel class I antiarrhythmic drug, were compared with flecainide in canine ventricular muscle by use of conventional microelectrode techniques. 2. At concentrations of 10(-6) M or higher, NIK-244 depressed the maximum rate of rise of depolarization (Vmax) significantly in a concentration-dependent manner. Also, the resting potential was depolarized at 10(-5) M. NIK-244 did not have any effect on the other action potential parameters or on the effective refractory period. 3. Flecainide significantly decreased Vmax at 3 x 10(-6) M or higher and the resting potential was depolarized at 10(-5) M. Like NIK-244, flecainide did not affect other action potential parameters. 4. NIK-244 and flecainide caused a use-dependent block of Vmax, and the rates of onset of inhibition at 3 Hz stimulation were 0.014 +/- 0.002 AP-1 at 2 x 10(-6) M NIK-244 and 0.021 +/- 0.012 AP-1 at 10(-5) M flecainide. Under the same conditions, the time constants of the recovery from use-dependent block were 27.1 +/- 13.3 s and 12.2 +/- 2.5 s for NIK-244 and flecainide, respectively. 5. These results suggest that NIK-244, like flecainide, should be classified as a slow kinetic drug and as Ic.
Satoh
H
H
Department of Pharmacology, Yamanashi Medical College, Japan.
Ishii
M
M
Hashimoto
K
K
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004285:Dogs; D004594:Electrophysiology; D005260:Female; D005424:Flecainide / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D010210:Papillary Muscles / Q000187:drug effects; D010640:Phenothiazines / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D010640:Phenothiazines; C046818:ethacizine; D005424:Flecainide