title: Lack of action potential-prolonging effect of terfenadine on rabbit myocardial tissue preparations.
abstract: The effects of terfenadine, an antiallergic drug also known for its QT-prolonging and arrhythmogenic activities, on the action potential of isolated myocardial tissue preparations from rabbits were examined with microelectrode techniques. In the Purkinje fibers and atrium, terfenadine concentration dependently decreased the maximum rate of rise (+.V(max)) without affecting other action potential parameters. In the ventricle, terfenadine had little effect on action potential configuration. In the sinoatrial node, terfenadine 20 microM prolonged cycle length mainly through inhibition of +.V(max). Terfenadine 1 microM completely inhibited the human ether a go-go-related gene (HERG) channel current expressed in HEK293 cells in the same experimental solution as in microelectrode experiments. The lack of terfenadine effect on the action potential duration suggests that there are drugs for which the HERG channel inhibitory action underlying in vivo QT prolongation cannot be evaluated based on their action potential-prolonging activity in isolated myocardial tissue preparations.
authors.affiliation: Department of Pharmacology, Toho University School of Pharmaceutical Sciences, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan.
authors.forename: Haruko
authors.initials: H
authors.lastname: Masumiya
authors.forename: Mariko
authors.initials: M
authors.lastname: Saito
authors.forename: Mie
authors.initials: M
authors.lastname: Ito
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Matsuda
authors.forename: Kazuo
authors.initials: K
authors.lastname: Noguchi
authors.forename: Naoko
authors.initials: N
authors.lastname: Iida-Tanaka
authors.forename: Hikaru
authors.initials: H
authors.lastname: Tanaka
authors.forename: Koki
authors.initials: K
authors.lastname: Shigenobu
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004562:Electrocardiography / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008839:Microelectrodes; D011690:Purkinje Fibers / Q000187:drug effects; D011817:Rabbits; D016593:Terfenadine / Q000494:pharmacology*
chemical_list: D018926:Anti-Allergic Agents; D018076:DNA, Complementary; D016593:Terfenadine