Effects of the antitussive drug cloperastine on ventricular repolarization in halothane-anesthetized Guinea pigs

Cloperastine is an antitussive drug,which can be received as an over-the-counter cold medicine. the chemical structure of cloperastine is quite similar to that of the antihistamine drug diphenhydramine,which is reported to inhibit herg k+ channels and clinically induce long qt syndrome after overdose. to analyze its proarrhythmic potential,we compared effects of cloperastine and diphenhydramine on the herg k+ channels expressed in hek293 cells. we further assessed their effects on the halothane-anesthetized guinea-pig heart under the monitoring of monophasic action potential (map) of the ventricle. cloperastine inhibited the herg k+ currents in a concentration-dependent manner with an ic50 value of 0.027 μm,whose potency was 100 times greater than that of diphenhydramine (ic 50; 2.7 μm). in the anesthetized guinea pigs,cloperastine at a therapeutic dose of 1 mg/kg prolonged the qt interval and map duration without affecting pr interval or qrs width. diphenhydramine at a therapeutic dose of 10 mg/kg prolonged the qt interval and map duration together with increase in pr interval and qrs width. the present results suggest that cloperastine may be categorized as a qt-prolonging drug that possibly induces arrhythmia at overdoses like diphenhydramine does. © the japanese pharmacological society.