Effects of the Antitussive Drug Cloperastine on Ventricular Repolarization in Halothane-Anesthetized Guinea Pigs

• Main Authors: Akira Takahara (Author), Kaori Fujiwara (Author), Atsushi Ohtsuki (Author), Takayuki Oka (Author), Iyuki Namekata (Author), Hikaru Tanaka (Author)
• Format: Book
• Published: Elsevier, 2012-01-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 1347-8613; 10.1254/jphs.12117FP
• Keywords: Therapeutics. Pharmacology; RM1-950
• Source: Journal of Pharmacological Sciences, Vol 120, Iss 3, Pp 165-175 (2012)

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. Keywords:: cloperastine, antitussive drug, hERG K+ channel, QT interval, monophasic action potential