Blockade of HERG channels expressed in Xenopus oocytes by the histamine receptor antagonists terfenadine and astemizole

Abstract

The widely used histamine receptor antagonists terfenadine and astemizole were shown to prolong the QT interval in electrocardiographic recordings in cases of overdose or inappropriate co‐medications, indicating a possible interaction with cardiac K⁺ channels. Here, terfenadine and astemizole both inhibited the human ether‐a‐go‐go related gene (HERG) encoded channels expressed in Xenopus oocytes at nanomolar concentrations in a use‐ and voltage‐dependent fashion. In contrast, inhibition of other delayed rectifier (Kvl.1 and I_sK) or inward rectifier K⁺ channels (IRK1) was much weaker and occurred only at high micromolar concentrations. These results suggest that blockade of HERG channels by terfenadine and astemizole might contribute to the cardiac side effects of these compounds.