title: The conventional antihistamine drug cyproheptadine lacks QT-interval-prolonging action in halothane-anesthetized guinea pigs: comparison with hydroxyzine.
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 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.
authors.affiliation: Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Toho University, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Naoki
authors.initials: N
authors.lastname: Omuro
authors.forename: Akira
authors.initials: A
authors.lastname: Takahara
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000758:Anesthesia; D000818:Animals; D003533:Cyproheptadine / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects*; D006168:Guinea Pigs; D006221:Halothane; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology; D006633:Histamine Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000145:classification / Q000494:pharmacology*; D006919:Hydroxyzine / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D007275:Injections, Intravenous; D008133:Long QT Syndrome / Q000139:chemically induced*
chemical_list: D006633:Histamine Antagonists; D003533:Cyproheptadine; D006919:Hydroxyzine; D006221:Halothane