cj-033466 and Arrhythmias--Cardiac

The blocking effect of three 5-HT(4) 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-HT(4) 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.

Topics: Aminopyridines; Arrhythmias, Cardiac; Benzamides; Cell Line; Cisapride; Electrophysiology; Ether-A-Go-Go Potassium Channels; Humans; Imidazoles; Inhibitory Concentration 50; Morpholines; Patch-Clamp Techniques; Serotonin 5-HT4 Receptor Agonists; Serotonin Receptor Agonists