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recently withdrawn from the market due to its potential to induce cardiac 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-à-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.