Journal of Pharmacological Sciences (Print Edition) 2012-01-01

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

Akira Takahara, Kaori Fujiwara, Atsushi Ohtsuki, Takayuki Oka, Iyuki Namekata, Hikaru Tanaka

Index: J. Pharmacol. Sci. 120(3) , 165-75, (2012)

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Abstract

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 (IC₅₀; 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.