Relationship of N-demethylation of amiflamine and its metabolite to debrisoquine hydroxylation polymorphism

Abstract

The metabolism of the new reversible A-selective monoamine oxidase inhibitor amiflamine was studied in relation to polymorphic debrisoquine hydroxylation in 24 healthy subjects. Amiflamine is metabolized by 2 consecutive N-demethylations. By construction of urinary recovery ratios analogous to debrisoquine 4-hydroxydebrisoquine, correlations between debrisoquine metabolic ratio and amiflamine demethylated metabolites were significant and consistent within slow and rapid debrisoquine hydroxylators. Debrisoquine hydroxylation and amiflamine N-demethylation might be under common genetic regulation.