Effects of bepridil on the electrophysiological properties of guinea-pig ventricular muscles

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Abstract
1 Effects of bepridil, a new antianginal and potential antiarrhythimic agent, on transmembrane action potentials of ventricular muscles were examined in isolated right ventricular papillary muscles of guinea-pig. 2 Bepridil at concentrations above 5 × 10−6m caused a dose-dependent decrease in both the maximum upstroke velocity (Vmax) and the action potential duration from the upstroke to 30% repolarization (APD30). On the other hand, the resting potential (RP), the amplitude of action potential (AMP), and the action potential duration from the upstroke to 90% repolarization (APD90) were not affected even at the highest concentration applied (10−5m). 3 The curves relating membrane potential and Vmax were shifted by bepridil at 5 × 10−6m along the voltage axis in the direction of more negative potentials. 4 The recovery kinetics of Vmax assessed by premature stimuli were definitely slowed by bepridil at above 10−6m. This effect was more pronounced with higher [K+]o(10 mm) than normal [K+]o(5 mm). 5 Bepridil at 5 × 10−6m caused a rate-dependent decrease of Vmax (use-dependent block) with rapid onset and offset, as did lidocaine. 6 Slow responses, which had been induced by isoproenaline (5 × 10−6m) in K+-depolarized preparations, were suppressed significantly by additional application of bepridil at 10−5m. 7 These findings suggest that bepridil has electrophysiological characteristics similar to those both of Class Ib and Class IV antiarrhythmic drugs.

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