期刊
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
卷 52, 期 6, 页码 494-499出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/FJC.0b013e31818eec8d
关键词
antitussive; clobutinol; hERG; QT prolongation; torsade de pointes
资金
- Evotec
A common over-the-counter (OTC) non-opioid antitussive drug, clobutinol, was recently withdrawn from the market due to its potential to induce cardiac arrhythmias by a blockade of the potassium channel coded by the human ether-a-go-go-related gene (hERG). In this study, we investigated the effects of a number of antitussive compounds on the hERG ion channel current using patch-clamp electrophysiology, and compared the effects to that of clobutinol. The compounds clobutinol, pentoxyverine, dextromethorphan, and codeine inhibited the outward current in hERG transfected cells with half-maximal inhibition concentrations (IC50) of 1-9 mu M, 3.0 mu M, 5.1 mu M, and 97 mu M, respectively. For the obromine, no significant effect on the hERG current at a concentration up to 100 mu M was detected. Safety margins between the effects of the drugs on the hERG ion channel current and their calculated maximal free therapeutic plasma concentration were calculated. These results were compared to assess potential risks of the compounds to induce torsade de pointes-type arrhythmias.
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