Comparison of the cardiac electrophysiologic effects of NE-10064 with sotalol and E-4031 and their modification by simulated ischaemia

The electrophysiologic effects of a new anti-arrhythmic 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.