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

The pharmacological characteristics of [H-3]dofetilide binding were examined in membranes prepared from human embryonic kidney (HEK293) cells stably expressing human ether-a-go-go related gene (HERG) K+ channels. The classIII antiarrhythmic compounds dofetilide, clofilium, 4 '-[[1-[2-(6-methyl-2-pyridyl)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 pimozide, terfenadine and haloperidol, all of which prolong the QT interval in man, also inhibited binding. These data indicate that a [H-3]dofetilide binding assay using HERG membranes may help identify compounds that prolong the QT interval. (C) 2001 Published by Elsevier Science B.V.