Abstract: Objective To investigate the effects of a novel coumarin piperidine antipsychotic (17m) on QTc interval in guinea pigs and Beagle dogs, and to evaluate its cardiac safety. Methods Guinea pigs were randomly divided into three groups: a vehicle group,a sotalol positive control (3 mg/kg) group, and 17m (0.6, 2, and 6 mg/kg) groups.After intraperitoneal injection of 1.5 g/kg urethane, guinea pigs were subjected to jugular vein catheterization for drug administration.The basal electrocardiogram (ECG) of guinea pigs was measured before administration. Then each group was intravenously infused with the corresponding dose of the drugs, and the vehicle group was infused with the volume of vehicle. The infusion was completed within 10 min.The ECG of guinea pigs was measured before and 180 min after administration, and peak of the QTc interval was calculated at each time point.According to weight and sex balance method, Beagle dogs were divided into three groups: a vehicle group, a risperidone (5 mg/kg) control group and 17m (10, 300 mg/kg) groups.Beagle dogs were given the corresponding drugs or vehicles once per day for seven consecutive days.The ECG of dogs were measured days 1 and 7 before dosing and 8 h after dosing, and the QTc interval values at different time points were calculated, so as to evaluate the effects of the drug on QTc interval. Results Compared with the baseline before administration (0 min) and the corresponding time points of the vehicle group, the positive control sotalol (3 mg/kg, i.v.) significantly prolonged the QTc interval of anesthetized guinea pigs (P<0.05 or P<0.01).Furthermore, 17m (0.6, 2, and 6 mg/kg)produced no significant effects on the QTc value of anesthetized guinea pigs (P>0.05). Compared with the baseline before administration (0 h) and the corresponding time point of the vehicle group, the QTc interval of Beagle dogs in the positive control group increased at different time points within 0 h-8 h after single and multiple administration of risperidone (P<0.05). However, there was no significant effect on QTc interval of Beagle dogs after single and multiple administrations of 17m (10 and 300 mg/kg) (P>0.05). Conclusions 17m cannot significantly prolong QTc interval in guinea pigs and Beagle dogs, which indicates that 17m may has low potential for prolonging the QTc interval in clinical practice, with good cardiac safety.