BLOCKADE OF HERG CHANNELS EXPRESSED IN XENOPUS OOCYTES BY THE HISTAMINE-RECEPTOR ANTAGONISTS TERFENADINE AND ASTEMIZOLE

The widely used histamine receptor antagonists terfenadine and astemiz ole were shown to prolong the QT interval in electrocardiographic reco rdings in cases of overdose or inappropriate co-medications, indicatin g a possible interaction with cardiac K+ channels. Here, terfenadine a nd astemizole both inhibited the human ether-a-go-go related gene (HER G) encoded channels expressed in Xenopus oocytes at nanomolar concentr ations in a use- and voltage-dependent fashion. In contrast, inhibitio n of other delayed rectifier (Kv1.1 and I-sK) or inward rectifier K+ c hannels (IRK1) was much, weaker and occurred only at high micromolar c oncentrations. These results suggest that blockade of HERG channels by terfenadine and astemizole might contribute to the cardiac side effec ts of these compounds.