Effects of TYB-3823, a new antiarrhythmic drug, on the electrophysiological properties of guinea-pig ventricular muscles.
1. The effects of TYB-3823 (B-GYKI 38233), a new antiarrhythmic drug, were electrophysiologically examined in the guinea-pig ventricular muscles. 2. TYB-3823 at concentrations of 1-3 x 10(-7) M significantly prolonged the action potential duration (APD) of the papillary muscle. However, the resting potential, action potential amplitude and maximum rate of depolarization (Vmax) were unaffected by the drug at such concentrations. At a higher concentration (1 x 10(-4) M) TYB-3823 reduced Vmax. 3. Voltage clamp experiments with single ventricular cells revealed that TYB-3823 at concentrations higher than 1 x 10(-7) M reduced the outward potassium currents, especially the time-dependent outward current, but that TYB-3823 failed to affect the calcium current. 4. These results suggested that TYB-3823 at low concentrations reduces the outward potassium current to give rise to a prolongation of APD and that at higher concentrations it additionally inhibits the sodium channels; both the effects may be related to the antiarrhythmic action of this drug.
Ohmura
T
T
Department of Pharmacology, Fukui Medical School, Japan.
Nishio
M
M
Kigoshi
S
S
Muramatsu
I
I
Momose
Y
Y
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004594:Electrophysiology; D006146:Guanidines / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000166:cytology; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology
D000889:Anti-Arrhythmia Agents; D006146:Guanidines; C059816:restacorin