3H]dofetilide binding to HERG transfected membranes: a potential high throughput preclinical screen.
K Finlayson, L Turnbull, C T January, J Sharkey, J S Kelly
Fujisawa Institute of Neuroscience, University of Edinburgh, 1 George Square, EH8 9JZ, Edinburgh, UK. Keith.Finlayson@ed.ac.uk
European journal of pharmacology 2001 Oct 26The pharmacological characteristics of [3H]dofetilide binding were examined in membranes prepared from human embryonic kidney (HEK293) cells stably expressing human ether-á-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-1H-benzimidazol-2-yl)amino]ethyl]-4-[(methylsulfonyl)amino]benzene-sulfonamide (WAY-123,398) and d-sotalol all inhibited [3H]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 [3H]dofetilide binding assay using HERG membranes may help identify compounds that prolong the QT interval.
Citation
K Finlayson, L Turnbull, C T January, J Sharkey, J S Kelly. 3H]dofetilide binding to HERG transfected membranes: a potential high throughput preclinical screen. European journal of pharmacology. 2001 Oct 26;430(1):147-8
Mesh Tags
Substances
PMID: 11698075
View Full Text
