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 butyrate. Intra-brain distribution of the esters reflected a pattern of AchE activity.
Irie
T
T
Division of Clinical Research, National Institute of Radiological Sciences, Chiba, Japan.
Fukushi
K
K
Akimoto
Y
Y
Tamagami
H
H
Nozaki
T
T
D000109:Acetylcholine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000378:metabolism*; D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000098:blood supply / Q000201:enzymology*; D002250:Carbon Radioisotopes / Q000737:chemistry / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D012039:Regional Blood Flow; D013379:Substrate Specificity
D002250:Carbon Radioisotopes; D000110:Acetylcholinesterase; D000109:Acetylcholine