Do astemizole and its metabolites block HERG potassium channels?
The potent HERG channel blockade by desmethylastemizole supports it as the principal cause of long QT syndrome in patients taking astemizole.
Desmethylastemizole and astemizole cause equipotent block of HERG channels, and these are among the most potent HERG channel antagonists yet studied. Because desmethylastemizole becomes the dominant compound in serum, these findings support the postulate that it becomes the principal cause of long QT syndrome observed in patients following astemizole ingestion. Norastemizole block of HERG channels is weaker; thus, the risk of producing ventricular arrhythmias may be lower. These findings underscore the potential roles of some H1-receptor antagonist metabolites as K+ channel antagonists.
Zhou et al. (Tue,) studied this question.
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