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1 CP-060S is a novel sodium and calcium overload inhibitor, and is also characterized as a calcium channel blocker. As these activities have each been shown independently to ameliorate ischaemia damage in the myocardium, the combination may synergistically exert cardioprotection. In this study, therefore, the protective e ect of CP-060S against ischaemia-and reperfusion-induced arrhythmia was evaluated in anesthetized rats. 2 Rats were anaesthetized with pentobarbitone, and the left anterior descending coronary artery was occluded for either 5 min with subsequent reperfusion (a reperfusion-induced arrhythmia model) or 30 min without (an ischaemia-induced arrhythmia model). All drugs were intravenously administered 1 min before the onset of occlusion. 3 In the reperfusion-induced arrhythmia model, the animals in the vehicle-treated group exhibited ventricular tachycardia (VT) in 100%, ventricular ®brillation (VF) in 89%, and death caused by sustained VF in 56%. CP-060S (30 ± 300 mg kg 71 ) dose-dependently suppressed the incidences of arrhythmias. Signi®cant decreases occurred at 100 mg kg 71 in VF (incidence: 42%) and mortality (8%), and at 300 mg kg 71 in VT (50%), VF (33%) and mortality (8%). This protective e ect of CP-060S was 10 times more potent than that of a pure calcium channel blocker, diltiazem (30 ± 1000 mg kg 71 ) we tested, in terms of e ective dose ranges. As both drugs decreased myocardial oxygen consumption estimated by rate-pressure product to a similar extent, the calcium channel blocking activity of CP-060S would not seem to be su cient to explain its potency. 4 In the same model, co-administration of ine ective doses of diltiazem (300 mg kg 71 ) and a sodium and calcium overload inhibitor, R56865 (100 mg kg 71 ), produced signi®cant suppression of VT (incidence: 62%), VF (46%) and mortality (8%). By contrast, co-administration of R56865 at the same dose with CP-060S (300 mg kg 71 ) did not add to the e ect of a single treatment of CP-060S. 5 In the ischaemia-induced arrhythmia model, CP-060S (300 mg kg 71 ) signi®cantly decreased the incidence of VF from 75% to 29%, whereas diltiazem (1 mg kg 71 ) was ine ective. 6 These results suggest that CP-060S inhibits both ischaemia-and reperfusion-induced arrhythmia. The combination of the calcium channel blocking e ect and the calcium overload inhibition was hypothesized to contribute to these potently protective e ects.