Summary: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 10−7-10−4M(cycle length, 2000 ms), resting potential and action potential duration (APD90) were not altered by the drug. Action potential amplitude and APD50were reduced (p < 0.01) by 10−4M, andVmaxwas reduced (p < 0.01) by EO-122 s 10−5M. The effect of EO-122 on Vmaxwas use-dependent. At 10−6and 10−5M(cycle length, 2000 ms), the time constant for onset of block (TON) 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, 10−5M,on the membrane currents in ventricular myocytes and found that the drug attenuated the slow inward current (Isi). EO-122 reduced peak Isiby 68.6 ± 5.2% (p < 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.