The Conventional Antihistamine Drug Cyproheptadine Lacks QT-interval–Prolonging Action in Halothane-Anesthetized Guinea Pigs: Comparison With Hydroxyzine

Abstract

Abstract. Antihistamines are known to belong to the chemical class that may induce long QT syndrome. Among them, cyproheptadine has been shown to exert multifaceted actions on the ventricular repolarization phase; namely, shortening of the action potential duration at supratherapeutic concentrations of 2 -8 mM and prolongation of the QT interval at ≥ 10 mM. Since information is limited regarding the in vivo electrophysiological effects of cyproheptadine, we assessed it using the halothane-anesthetized guinea-pig model, which was compared with effects of another antihistamine drug, hydroxyzine. Sub-therapeutic to therapeutic doses of hydroxyzine at 1 and 10 mg/kg, i.v. prolonged the QT interval and duration of monophasic action potential, whereas therapeutic to supra-therapeutic doses of cyproheptadine at 0.1 and 1 mg/kg, i.v. hardly affected the indices of ventricular repolarization. These results suggest that cyproheptadine may be categorized into antihistamines with little effect on the ventricular repolarization.

Safety of Cyproheptadine, an Orexigenic Drug. Analysis of the French National Pharmacovigilance Data-Base and Systematic Review

“…All of these AEs disappeared after cyproheptadine discontinuation. In in vivo and in vitro studies, cyproheptadine did not induce cardiovascular AE complications ( 118 ), which were reported mainly with other H1-antagonists such as diphenhydramine and hydroxyzine ( 14 ).…”