Synthesis and evaluation of 11C- and 18F-labeled 1-[2-(4-alkoxy-3-methoxyphenyl)ethyl]-4-(3-phenylpropyl)piperazines as sigma receptor ligands for positron emission tomography studies.
We prepared sigma(1)-receptor selective 1-([4-methoxy-(11)C]-3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine ([(11)C]SA4503) and its fluorinated analog 1-([4-methoxy-(11)C]3,4-dimethoxyphenethyl)-4-[3-(4-fluorophenyl)propyl]piperazine ([(11)C]SA5845), and their [(11)C]ethoxy and [(18)F]fluoroethoxy analogs, and evaluated their potential for positron emission tomography studies. [(11)C]SA4503 is most selective for sigma(1) receptors, and the other five showed affinities for sigma(1) and sigma(2) receptors with a different extent. All radioligands showed the receptor-specific binding in the brain, and visualized similar regional brain distributions by ex vivo autoradiography. The [(11)C]ethoxy analogs were relatively labile for metabolism.
Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan. kawamura@pet.tmig.or.jp
Kazunori
K
Kawamura
Philip H
PH
Elsinga
Tadayuki
T
Kobayashi
Shin-ichi
S
Ishii
Wei-Fang
WF
Wang
Kiyoshi
K
Matsuno
Willem
W
Vaalburg
Kiichi
K
Ishiwata
D000818:Animals; D006168:Guinea Pigs; D008297:Male; D051379:Mice; D018697:Nootropic Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics; D010879:Piperazines / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D017480:Receptors, sigma / Q000819:agonists / Q000378:metabolism; D013329:Structure-Activity Relationship; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
D018697:Nootropic Agents; D010879:Piperazines; D017480:Receptors, sigma; C101789:SA 4503