Abstract: Objective To study 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 the vehicle group, the positive control group of sotalol ( 3 mg/kg), and the 17m (0.6, 2, 6 mg/kg) groups. After intraperitoneal injection of 1.5g /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 infusion was completed within 10 min. The ECG of guinea pigs was measured before and 180 min after administration, and the QTc interval were calculated at each time point. Beagle dogs were divided into the vehicle group, the risperidone control group (5 mg/kg) and the 17m (10, 300 mg/kg) groups according to their weight and gender. Beagle dogs were given the appropriate drugs or vehicles once a day for 7 days. The ECG of dogs were measured separately before and after 8 h of dosing at day 1 and day 7, and the QTc interval values at different time points were calculated to evaluate the effects of drugs on QTc interval. Results Compared with the pre-dose baseline value (0 min) and the corresponding time points of the vehicle group, the positive control drug sotalol (3 mg/kg, i.v.) significantly prolonged the QTc interval of anesthetized guinea pigs (P<0.05, P<0.01). While compound 17m (0.6, 2, 6 mg/kg) has no significant effect on the QTc value of anesthetized guinea pigs (P>0.05). Compared with the pre-dose baseline value (0 h) and the corresponding time point of vehicle group, the QTc interval of Beagle dogs in the positive control group was 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, 300 mg/kg) (P>0.05). Conclusions 17m has no significant prolongation effect on QTc interval in guinea pigs and Beagle dogs. It is suggested that 17m may has low potential for prolonging the QTc interval in clinical practice.