The 5-HT4 agonists cisapride, mosapride, and CJ-033466, a novel potent compound, exhibit different human Ether-a-go-go-Related Gene (hERG)-blocking activities

Abstract

The blocking effect of three 5-HT4 agonists, cisapride, mosapride, and the newly discovered CJ-033466 on the human ether-a-go-go-related gene (hERG) channel was studied using a whole cell patch-clamp technique in HEK293 cells. Cisapride was found to be the most potent of the hERG blockers. CJ-033466 had the widest safety margin between its hERG blocking activity and 5-HT4 agonism among the tested compounds. This suggests a lower clinical risk of cardiac arrhythmia in CJ-033466 compared with the other 2 agonists. Therefore, CJ-033466 has the potential to be a drug with higher therapeutic efficacy and less cardiac risk than both cisapride and mosapride. ©2007 The Japanese Pharmacological Society.