[3H]dofetilide binding to HERG transfected membranes:: a potential high throughput preclinical screen
[3H]dofetilide binding to HERG transfected membranes:: a potential high throughput preclinical screen
复制标题
DOI：
10.1016/s0014-2999(01)01362-0
复制
发表时间：
2001-10-26
影响因子：
5
通讯作者：
Kelly, JS
中科院分区：
文献类型：
--
作者：
Finlayson, K;Turnbull, L;Kelly, JS
研究了[H-3]多非利特在稳定表达人乙醚相关基因（HERG） K+通道的人胚胎肾（HEK293）细胞制备的膜中结合的药理学特性。ⅱ类抗心律失常化合物dofelide、clofilium、4′-[[1-[2-（6-甲基-2-吡啶基）乙基]-4-胡椒基]羰基]甲磺酰苯胺（E-4031）、n -甲基- n -[2-[甲基- 1- h -苯并咪唑-2-基)氨基]乙基]-4-[（甲基磺酰基）氨基]苯磺酰胺（WAY- 123,398）和d-sotalol均抑制[H-3] dofelide结合。此外，结构无关的化合物吡莫齐、特非那定和氟哌啶醇均能延长男性QT间期，也能抑制结合。这些数据表明，使用HERG膜的[H-3]多非利特结合试验可能有助于识别延长QT间期的化合物。(C) 2001年Elsevier Science B.V.出版
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.