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

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  • Kobayashi Kazuko
    Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Toho University, Japan Department of Pharmacy, Toho University Sakura Medical Center, Japan
  • Omuro Naoki
    Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Toho University, Japan
  • Takahara Akira
    Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Toho University, Japan

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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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