Effects of common antitussive drugs on the hERG potassium channel current
| Autor: | Rainer Netzer, Nadine Ahrens, Irene Schlobohm, Clemens Möller, Christian Kirchhoff, Heike Deisemann |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities ERG1 Potassium Channel Time Factors hERG CHO Cells Cyclopentanes Pharmacology Transfection Dextromethorphan Membrane Potentials chemistry.chemical_compound Cricetulus Torsades de Pointes Cricetinae medicine Potassium Channel Blockers Animals Humans cardiovascular diseases Theobromine Ion channel Membrane potential biology Dose-Response Relationship Drug Chemistry Codeine Pentoxyverine Amino Alcohols Potassium channel Ether-A-Go-Go Potassium Channels Antitussive Agents biology.protein Potassium Clobutinol Cardiology and Cardiovascular Medicine medicine.drug |
| Zdroj: | Journal of cardiovascular pharmacology. 52(6) |
| ISSN: | 1533-4023 |
| Popis: | A common over-the-counter (OTC) non-opioid antitussive drug, clobutinol, was recently withdrawn from the market due to its potential to induce cardiac arrhythmias by a blockade of the potassium channel coded by the human ether-a-go-go-related gene (hERG).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 microM, 3.0 microM, 5.1 microM, and 97 microM, respectively. For theobromine, no significant effect on the hERG current at a concentration up to 100 microM 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|