title: Blockade of HERG channels expressed in Xenopus oocytes by the histamine receptor antagonists terfenadine and astemizole.
abstract: The widely used histamine receptor antagonists terfenadine and astemizole were shown to prolong the QT interval in electrocardiographic recordings in cases of overdose or inappropriate co-medications, indicating a possible interaction with cardiac K+ channels. Here, terfenadine and astemizole both inhibited the human ether-a-go-go related gene (HERG) encoded channels expressed in Xenopus oocytes at nanomolar concentrations in a use- and voltage-dependent fashion. In contrast, inhibition of other delayed rectifier (Kv1.1 and IsK) or inward rectifier K+ channels (IRK1) was much weaker and occurred only at high micromolar concentrations. These results suggest that blockade of HERG channels by terfenadine and astemizole might contribute to the cardiac side effects of these compounds.
authors.affiliation: Physiologisches Institut I, Eberhard-Karls-Universität Tübingen, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Suessbrich
authors.forename: S
authors.initials: S
authors.lastname: Waldegger
authors.forename: F
authors.initials: F
authors.lastname: Lang
authors.forename: A E
authors.initials: AE
authors.lastname: Busch
mesh_terms: D000818:Animals; D016589:Astemizole / Q000494:pharmacology*; D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; D000072237:ERG1 Potassium Channel; D004553:Electric Conductivity; D051638:Ether-A-Go-Go Potassium Channels; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D051662:Kv1.1 Potassium Channel; D008564:Membrane Potentials; D009865:Oocytes; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000096:biosynthesis / Q000187:drug effects* / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated; D016593:Terfenadine / Q000494:pharmacology*; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D014981:Xenopus
chemical_list: D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; C072312:ERG protein, human; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D006634:Histamine H1 Antagonists; C496946:KCNA1 protein, human; C000606913:KCNH2 protein, human; C092509:KCNH6 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; C059983:potassium channel protein I(sk); D051662:Kv1.1 Potassium Channel; D016593:Terfenadine; D016589:Astemizole; D011188:Potassium