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

摘要: QT prolongation, a risk factor for arrhythmias, can result from genetic variants in one (or more) of the genes governing cardiac repolarization as well intake drugs known to affect K(+) channel encoded by human ether-a-go-go-related gene (HERG). In this paper, we will report case drug-induced long syndrome associated with an H(1)-receptor antagonist, hydroxyzine, which mutation was identified HERG gene. After taking 75 mg hydroxyzine several days, 34-year-old female began experience repetitive syncope. The deleterious effect suspected because QTc interval shortened 630 464 ms after cessation drug. Later on, patient found harbor A614V-HERG mutation. By using patch-clamp technique heterologous expression system, examined functional outcome A614V and confirmed dominant-negative on expression. Hydroxyzine concentration-dependently inhibited both wild-type (WT) WT/A614V-HERG currents. Half-maximum block concentrations WT currents were 0.62 0.52 microM, respectively. Thus, accidental combination appeared have led severe phenotype, probably, syncope due torsade de pointes.