Deuterium Kinetic Isotope Effect Studies of a Potential in Vivo Metabolic Trapping Agent for Monoamine Oxidase B.

ABSTRACT: Visualizing the in vivo activity of monoamine oxidase B (MAO-B) is a valuable tool in the ongoing investigation of astrogliosis in neurodegeneration. Existing strategies for imaging changes in MAO enzyme expression or activity have utilized the irreversible suicide inhibitors or high-affinity reversibly binding inhibitors as positron emission tomography (PET) ligands. As an alternative approach, we developed 4-methyl-7-[(1-[¹¹C]methyl-1,2,3,6-tetrahydropyridin-4-yl)oxy]-2 H-chromen-2-one ([¹¹C]Cou) as a metabolic trapping agent for MAO-B. Trapping of [¹¹C]Cou in rhesus monkey brain demonstrated MAO-B selectivity. In this work, we have attempted to improve on the in vivo pharmacokinetics of [¹¹C]Cou by using the deuterium kinetic isotope effect (K

SUBMITTER: Drake LR 

PROVIDER: S-EPMC7589526 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature