Supplementary Material for: Additive inhibition of HERG channels expressed in Xenopus oocytes by antipsychotic drugs and citrus juice flavonoid naringenin

Background: Citrus juice has been shown to cause QT prolongation in electrocardiograms of healthy volunteers and naringenin, a major flavonoid found in citrus juice, has been identified as the potent inhibitor HERG channels as the cause of QT prolongation. Several antipsychotic drugs such as haloperidol, chlorpromazine, and clozapine, have also been reported to inhibit HERG channels and prolong QT interval in patients using these drugs. However, the interaction between naringenin and antipsychotic drugs on the function of HERG channels has not been studied. Methods: In the present study, we evaluated the effect of combining naringenin with antipsychotics on the function of HERG channels expressed in Xenopus oocytes. Results: When 30 µM naringenin was added to antipsychotic drugs (1 µM haloperidol, 10 µM chlorpromazine, or 10 µM clozapine), significantly greater HERG inhibition was demonstrated, compared to the inhibition caused by antipsychotic drugs alone. Conclusion: The results indicate that an additive interaction occurs between naringenin and antipsychotics. This additive HERG inhibition could pose an increased risk of arrhythmias by decreasing repolarization reserve and possible repolarization heterogeneity.