Epinastine, a nonsedating histamine H1 receptor antagonist, has a negligible effect on HERG channel.
Terfenadine and astemizole rarely cause cardiac arrhythmias by suppressing the cardiac rapid delayed rectifier K+ channel encoded by the human ether-a-go-go-related gene (HERG). Epinastine, however, has not been reported to have the adverse effect. We have therefore compared the effects of epinastine, terfenadine and astemizole on HERG channels expressed in Xenopus oocytes. Terfenadine and astemizole suppressed the HERG current with IC50 of 431 nM and 69 nM, respectively. In contrast, 100 microM epinastine inhibited the HERG current by only 11+/-2.1%. These results may provide an explanation for the difference in the cardiotoxicity between different nonsedating histamine H1 receptor antagonists.
Chachin
M
M
Department of Pharmacology, Kawanishi Pharma Research Institute, Nippon Boehringer Ingelheim, Japan.
Katayama
Y
Y
Yamada
M
M
Horio
Y
Y
Ohmura
T
T
Kitagawa
H
H
Uchida
S
S
Kurachi
Y
Y
D000818:Animals; D016589:Astemizole / Q000494:pharmacology; D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; D003984:Dibenzazepines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D015870:Gene Expression / Q000187:drug effects; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects* / Q000235:genetics; D024642:Potassium Channels, Voltage-Gated; D016593:Terfenadine / Q000494:pharmacology; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D014981:Xenopus
D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; D003984:Dibenzazepines; C072312:ERG protein, human; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D006634:Histamine H1 Antagonists; D007093:Imidazoles; C000606913:KCNH2 protein, human; C092509:KCNH6 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D016593:Terfenadine; D016589:Astemizole; C053090:epinastine