Epinastine, a nonsedating histamine H-1 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 h ave the adverse effect. We have therefore compared the effects of epinastin e, terfenadine and astemizole on HERG channels expressed in Xenopus oocytes . Terfenadine and astemizole suppressed the HERG current with IC50 of 431 n M and 69 nM, respectively. In contrast, 100 mu M epinastine inhibited the H ERG current by only 11 +/- 2.1%. These results may provide an explanation f or the difference in the cardiotoxity between different nonsedating histami ne H-1 receptor antagonists. (C) 1999 Elsevier Science B.V. All rights rese rved.