[H-3]dofetilide binding to HERG transfected membranes: a potential high throughput preclinical screen

The pharmacological characteristics of [H-3]dofetilide binding were examine d in membranes prepared from human embryonic kidney (HEK293) cells stably e xpressing human ether-a-go-go related gene (HERG) K+ channels. The classIII antiarrhythmic compounds dofetilide, clofilium, 4 '-[[1-[2-(6-methyl-2-pyr idyl)ethyl]-4-piperidyl]carbonyl]methanesulfonanilide (E-4031), N-methyl-N- [2-[methyl-(1-methyl- 1 H-benzimidazol-2-yl)amino]ethyl]-4-[(methylsulfonyl )amino]benzene-sulfonamide (WAY- 123,398) and d-sotalol all inhibited [H-3] dofetilide binding. In addition, the structurally unrelated compounds pimoz ide, terfenadine and haloperidol, all of which prolong the QT interval in m an, also inhibited binding. These data indicate that a [H-3]dofetilide bind ing assay using HERG membranes may help identify compounds that prolong the QT interval. (C) 2001 Published by Elsevier Science B.V.