Effects of TYB-3823, a new antiarrhythmic drug, on the electrophysiological properties of guinea-pig ventricular muscles

Abstract

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 × 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 ( V · max ) were unaffected by the drug at such concentrations. At a higher concentration (1 × 10 −4 M) TYB-3823 reduced V · max . 3. Voltage clamp experiments with single ventricular cells revealed that TYB-3823 at concentrations higher than 1 × 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.