ABSTRACT: Electrophysiological effects of bisaramil, a novel antiarrhythmic agent, were examined using the conventional microelectrode technique applied to cardiac multicellular preparations from guinea-pigs, rabbits and dogs and the whole-cell patch-clamp technique applied to guinea-pig ventricular myocytes. Bisaramil at 10–6 M or higher concentrations produced a dose-dependent decrease in the maximum rate of rise (
max) of action potentials of guinea-pig papillary muscles without changes in resting membrane potentials. In the presence of bisaramil, trains of stimuli at rates > 0.1 Hz led to the use-dependent block of
max, which was enhanced at higher frequencies. At a concentration of 3 10–6 M, the degree of use-dependent block was about 35% at 3.3 Hz, of which degree was comparable to those of 10–4 M disopyramide and lidocaine. The development of
max block by bisaramil was expressed by a single exponential function in the same manner as flecainide, whereas the time courses of the block development by disopyramide and lidocaine were described by two exponentials. Recovery time constants from Vmax block were 44.13.4 s and 20.32.3 s for bisaramil and flecainide, respectively. Bisaramil at 10–6 and 3 10–6 M did not change the action potential duration of guinea-pig papillary muscles and rabbit atrial muscles with a significant reduction of
max. No change in action potential duration can be explained by depression of both the Ca2+ and the delayed outward K+ currents by bisaramil. On the other hand, 10–6 M bisaramil shortened action potential duration of canine Purkinje fibers at 50% and 90% of repolarization. In addition, bisaramil (3 10–6 M) suppressed sinus node automaticity, which agreed with voltage clamp studies indicating that bisaramil directly suppressed the calcium channel. These results suggest that bisaramil may be classified as class Ic agent showing a slow kinetic and potent action on the sodium channel.
Archiv für Experimentelle Pathologie und Pharmakologie 08/1991; 344(3):323-330. · 2.65 Impact Factor