Cercainide

The electrophysiological effects of CRE‐1087, a new antiarrhythmic drug, were studied in guinea‐pig papillary muscles.CRE‐1087 (10−7m‐10−4m) produced a concentration‐dependent decrease in the action potential amplitude and Vmax of the upstroke without altering the action potential duration or the resting membrane potential.At 5 × 10−6m, CRE‐1087 produced a 5.0 ± 1.0% tonic Vmax block and this value was not modified at the different rates of stimulation tested. In the presence of CRE‐1087, trains of stimuli at rates between 0.5 and 3 Hz led to an exponential decline in Vmax (frequency‐dependent Vmax block) which augmented at higher rates of stimulation. At 2 Hz the onset kinetics of the frequency‐dependent Vmax block was fitted by a monoexponential function being the K value 0.099 ± 0.012 AP−1. The time constant for the recovery of Vmax from the frequency‐dependent block was prolonged to 18.3 ± 1.5 s.CRE‐1087 (5 × 10−6m) did not shift the membrane responsiveness curve.CRE‐1087 had no effect on the characteristics of the slow action potentials elicited by isoprenaline in ventricular fibres depolarized by 27 mm KCl, which suggested that CRE‐1087 did not exhibit class IV (Ca antagonist) antiarrhythmic actions.6 The slow onset and the slow offset kinetics of frequency‐dependent Vmax block during repetitive activity suggested that in guinea‐pig ventricular muscle fibres CRE‐1087 exhibited class Ic antiarrhythmic actions.