Key result
Intravenous administration of cyproheptadine at 0.1 and 1 mg/kg did not prolong the QT interval or monophasic action potential duration in guinea pigs, whereas hydroxyzine significantly prolonged both.
Why the study?
Does cyproheptadine affect ventricular repolarization compared to hydroxyzine in halothane-anesthetized guinea pigs?
Does cyproheptadine affect ventricular repolarization compared to hydroxyzine in halothane-anesthetized guinea pigs?
Cyproheptadine, unlike hydroxyzine, does not significantly prolong the QT interval at therapeutic to supra-therapeutic doses in an in vivo guinea pig model.
Answers are grounded in this paper and cite their sources.
Hypothesis-generating for lower QT liability with cyproheptadine versus hydroxyzine; leaves open translation to human repolarization risk.
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 supra-therapeutic concentrations of 2 - 8 μM and prolongation of the QT interval at ≥ 10 μM. 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.
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Kobayashi et al. (2013) studied Healthy (Animal Model for QT Prolongation) (n=12). Cyproheptadine vs. Hydroxyzine (1 and 10 mg/kg intravenously) was evaluated on Change in QT interval and monophasic action potential duration (MAP90). Intravenous administration of cyproheptadine at 0.1 and 1 mg/kg did not prolong the QT interval or monophasic action potential duration in guinea pigs, whereas hydroxyzine significantly prolonged both.
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