Hydroxyzine, a First Generation H1-Receptor Antagonist, Inhibits Human Ether-a-go-go-Related Gene (HERG) Current and Causes Syncope in a Patient With the HERG Mutation
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概要
- 論文の詳細を見る
QT prolongation, a risk factor for arrhythmias, can result from genetic variants in one (or more) of the genes governing cardiac repolarization as well as intake of drugs known to affect a cardiac K+ channel encoded by human ether-a-go-go–related gene (HERG). In this paper, we will report a case of drug-induced long QT syndrome associated with an H1-receptor antagonist, hydroxyzine, in which a mutation was identified in the HERG gene. After taking 75 mg of hydroxyzine for several days, a 34-year-old female began to experience repetitive syncope. The deleterious effect of hydroxyzine was suspected because QTc interval shortened from 630 to 464 ms after cessation of the drug. Later on, the patient was found to harbor an A614V-HERG mutation. By using the patch-clamp technique in the heterologous expression system, we examined the functional outcome of the A614V mutation and confirmed a dominant-negative effect on HERG expression. Hydroxyzine concentration-dependently inhibited both wild-type (WT) and WT/A614V-HERG K+ currents. Half-maximum block concentrations of WT and WT/A614V-HERG K+ currents were 0.62 and 0.52 μM, respectively. Thus, accidental combination of genetic mutation and intake of hydroxyzine appeared to have led to a severe phenotype, probably, syncope due to torsade de pointes.
- 公益社団法人 日本薬理学会の論文
著者
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Ashihara Takashi
Department Of Cardiovascular And Respiratory Medicine Heart Rhythm Center Shiga University Of Medica
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MATSUURA Hiroshi
Division of Physiology, Shiga University of Medical Science
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Nagaoka Iori
Department Of Cardiology Shiga University Of Medical Science
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Takeyama Youichi
Division Of Cardiology Department Of Internal Medicine Showa University Fujigaoka Hospital
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Yumoto Yoshihiro
Department Of Cardio-angiology Kitasato University
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Tsuji Keiko
Department Of Cardiovascular And Respiratory Medicine Shiga University Of Medical Science
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Zenda Naoko
Division Of Cardiology Showa University Fujigaoka Hospital
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Higashi Yukei
Division Of Cardiology Department Of Internal Medicine Showa University Fujigaoka Hospital
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Sakaguchi Tomoko
Department Of Cardiovascular And Respiratory Medicine Shiga University Of Medical Science
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Oka Yuko
Department Of Cardiovascular And Respiratory Medicine Shiga University Of Medical Science
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Horie Minoru
Department Of Cardiac Physiology National Cardiovascular Center Research Institute
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Ding Wei-guang
Division Of Physiology Shiga University Of Medical Science
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Itoh Hideki
Department Of Anesthesiology And Critical Care Medicine Yokohama City University Graduate School Of
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Ding Wei-Guang
Division of Physiology, Shiga University of Medical Science, Japan
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ITO Makoto
Department of Bioresources, Faculty of Agriculture, Ehime University
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Zenda Naoko
Division of Cardiology, Showa University Fujigaoka Hospital, Japan
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Oka Yuko
Department of Cardiovascular Medicine, Shiga University of Medical Science, Japan
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Nagaoka Iori
Department of Cardiovascular Medicine, Shiga University of Medical Science, Japan
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Horie Minoru
Department of Cardiovascular Medicine, Shiga University of Medical Science, Japan
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Itoh Hideki
Department of Cardiovascular Medicine, Shiga University of Medical Science, Japan
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Matsuura Hiroshi
Division of Physiology, Shiga University of Medical Science, Japan
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