Design and Evaluation of Radioactive Acetylcholine Analogs for Mapping Brain Acetylcholinesterase (AchE) In Vivo

For mapping brain acetylcholinesterase (AchE) in vivo. seven radioactive acetylcholine analogs, N-[14C]methylpiperidyl-3- and 4-acetates, propionates, isobutyrates, and 3-butyrate were newly synthesized and evaluated in mice. The esters readily entered the brain and were hydrolyzed into the hydrophilic metabolite, which was trapped. In brain homogenates, the esters showed a wide range of enzymatic reactivity (about 40-fold), and high specificity for AchE (more than 82%) except the butrate. Intra-brain distribution of the esters reflected a pattern of AchE activity