Effects of common antitussive drugs on the hERG potassium channel current.

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Deisemann H, Ahrens N, Schlobohm I, Kirchhoff C, Netzer R, Moller C

Effects of common antitussive drugs on the hERG potassium channel current.

J Cardiovasc Pharmacol. 2008 Dec;52(6):494-9. doi: 10.1097/FJC.0b013e31818eec8d.

PubMed ID

19034038 [ View in PubMed

]

Abstract

A common over-the-counter (OTC) non-opioid antitussive drug, clobutinol, was recently withdrawn from the market due to its potential to induce cardiac arrhythmias by a blockade of the potassium channel coded by the human ether-a-go-go-related gene (hERG).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.

DrugBank Data that Cites this Article

Drugs

Pentoxyverine

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Pentoxyverine	Potassium voltage-gated channel subfamily H member 2	Protein	Humans	Unknown	Inhibitor	Details