Electrophysiological effects of a novel antiarrhythmic drug, EO-122, on guinea pig ventricular muscle and isolated myocytes.

EO-122, a newly developed structural analog of lidocaine, has recently been shown to suppress ventricular arrhythmias in a few clinical studies in patients and in experimental animals. In the present study, we investigated the effects of EO-122 on the electrophysiological properties of guinea pig papillary muscle and ventricular myocytes by means of standard microelectrode and whole-cell recording techniques, respectively, At the concentration range of 10(-7)-10(-4) M (cycle length, 2000 ms), resting potential and action potential duration (APD90) were not altered by the drug. Action potential amplitude and APD50 were reduced (p less than 0.01) by 10(-4) M, and Vmax was reduced (p less than 0.01) by EO-122 greater than or equal to 10(-5) M. The effect of EO-122 on Vmax was use-dependent. At 10(-6) and 10(-5) M (cycle length, 2000 ms), the time constant for onset of block (tau on) was 37.0 +/- 13.2 and 26.0 +/- 3.4 s, respectively. The recovery kinetics from use-dependent block was not monoexponential, and the estimated "time constant" for recovery was 76.5 s. We examined the effects of EO-122, 10(-5) M, on the membrane currents in ventricular myocytes and found that the drug attenuated the slow inward current (Isi). EO-122 reduced peak Isi by 68.6 +/- 5.2% (p less than 0.005), whereas the outward current was unchanged. The present study demonstrates that EO-122 blocks both the fast inward (Na+) and the slow inward (Ca2+) channels, and these effects are probably responsible for the antiarrhythmic effects of the drug.