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Comparison of the Cardiac Electrophysiologic Effects of NE-10064 with Sotalol and E-4031 and Their Modification by Simulated Ischaemia

Summary: The electrophysiologic effects of a new antiarrhythmic agent NE-10064 were compared with known class III drugs, E-4031 and sotalol, in sheep Purkinje fibres paced at 1 Hz under normal and simulated ischaemic conditions. NE-10064 0.3–3 μM and sotalol 0.3–300 μM prolonged action potential duration at 90% of repolarization (APD90) and effective refractory period (ERP) concentration dependently without affecting APD50 under normal conditions. E-4031 0.3–300 μM prolonged APD50, APD90, and ERP concentration dependently. Percentage increases in APD90 of 20 ± 6, 27 ± 6, and 33 ± 9 were calculated for NE-10064 3 μM, sotalol 300 μM, and E-4031 1 μM under normal conditions, respectively. The concentration–response curves for all three drugs were shifted to the right under simulated ischaemic conditions. The shift was more marked for NE-10064 and sotalol. Percentage increases in APD90 of 8 ± 5, 13 ± 2, and 23 ± 4 were observed with NE-10064 3 μM, sotalol 300 μM, and E-4031 1 μM during simulated ischaemia. NE-10064 exhibits electrophysiologic characteristics similar to those of known class III agents. Its ability to prolong APD90 under normal conditions may explain its antiarrhythmic action in vivo.