Disease relevance of Desmethylastemizole

• Torsade de pointes with an antihistamine metabolite: potassium channel blockade with desmethylastemizole [1].
• 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 [2].

High impact information on Desmethylastemizole

• RESULTS: Desmethylastemizole produced action potential prolongation and the induction of plateau early afterdepolarizations [1].
• Desmethylastemizole is formed in the human microsomal systems of the small intestine as well as the liver, which suggests the role of cytochromes P450 (P450s) in the first-pass metabolism of astemizole [3].
• CONCLUSIONS: Desmethylastemizole and astemizole cause equipotent block of HERG channels, and these are among the most potent HERG channel antagonists yet studied [2].
• The systemic bioavailability of desmethylastemizole was also increased [4].
• All the metabolites of astemizole tested i.e., desmethylastemizole, 6-hydroxydesmethylastemizole and norastemizole, were more active than astemizole in inhibiting the contraction of the ileum as well as the bronchoconstriction induced by histamine in guinea pigs [5].

Chemical compound and disease context of Desmethylastemizole

• We report the clinical observation of QT prolongation and torsade de pointes in a patient with undetectable serum concentrations of astemizole (< 0.5 ng/ml) and "therapeutic" concentrations of desmethylastemizole (up to 7.7 ng/ml or 17.3 nmol/liter) [1].

Anatomical context of Desmethylastemizole

• METHODS: The perforated patch clamp recording technique was used to study the effects of desmethylastemizole (20 nmol/liter) on action potentials and iKr in isolated rabbit ventricular myocytes [1].

References