title: Synthesis and evaluation of 1-(1-[5-(2'-[18F]fluoroethyl)-2-thienyl]-cyclohexyl)piperidine as a potential in vivo radioligand for the NMDA receptor-channel complex.
abstract: 1-(1-[5-(2'-[18F]Fluoroethyl)-2-thienyl]cyclohexyl)piperidine (18FE-TCP) was prepared as a fluorine-substituted analogue of the potent NMDA receptor channel blocker, 1-[1-(2-thienyl)cyclohexyl]piperidine (TCP), by the mesylate displacement with [18F]fluoride ion with isolated radiochemical yields of 6-12%, and the synthesis time including a two step HPLC purification was 120 min. The regional distribution in rat brain after i.v. injection of 18FE-TCP was heterogeneous and similar to the known distribution of phencyclidine recognition sites, with hippocampus-cerebellum, striatum-cerebellum and cerebral cortex-cerebellum concentration ratios of 2.08, 1.7 and 1.54, respectively, 15 min post-injection. Furthermore, this localized regional cerebral distribution was blocked by co-injection with the unlabelled FE-TCP or pretreatment with cis-2-hydroxymethyl-r-1-(N-piperidyl)-1-(2-thienyl)cyclohexane, with the greatest reductions seen in the hippocampus followed by the striatum and cerebral cortex. However, relatively low receptor binding affinity and high non-specific binding due to its high lipophilicity suggest that 18FE-TCP may not be a suitable radioligand for in vivo PET investigations of the NMDA receptor-channel complex.
authors.affiliation: Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Orita
authors.forename: S
authors.initials: S
authors.lastname: Sasaki
authors.forename: M
authors.initials: M
authors.lastname: Maeda
authors.forename: A
authors.initials: A
authors.lastname: Hashimoto
authors.forename: T
authors.initials: T
authors.lastname: Nishikawa
authors.forename: T
authors.initials: T
authors.lastname: Yugami
authors.forename: K
authors.initials: K
authors.lastname: Umezu
mesh_terms: D000818:Animals; D005462:Fluorine Radioisotopes; D008297:Male; D010622:Phencyclidine / Q000031:analogs & derivatives / Q000378:metabolism; D010880:Piperidines / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000032:analysis* / Q000037:antagonists & inhibitors*; D013876:Thiophenes / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
chemical_list: D005462:Fluorine Radioisotopes; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D013876:Thiophenes; C084454:1-(1-(5-(2'-fluoroethyl)-2-thienyl)-cyclohexyl)piperidine; C012058:tenocyclidine; D010622:Phencyclidine