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. Keywords:: human ether-a-go-go-related gene (hERG), 5-HT4 agonist, patch-clamp