title: In vivo receptor labeling of peripheral benzodiazepine receptor by ex vivo binding of [3H]PK11195.
abstract: In vivo receptor labeling of the peripheral benzodiazepine receptor was investigated using ex vivo binding of [3H]-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline-carb ox-amide ([3H]PK11195). In autoradiographic studies, high level specific binding of [3H]PK11195 was observed in the olfactory bulb. Intravenous administration of PK11195 dose-dependently (0.03-3 mg/kg) inhibited ex vivo binding of [3H]PK11195 in the olfactory bulb. Likewise, N-(2,5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)acetamide (DAA1106), a newly identified peripheral benzodiazepine receptor-specific ligand, dose-dependently (0.1-100 mg/kg) reduced ex vivo binding of [3H]PK11195, when administered intraperitoneally. In contrast, clonazepam, a central benzodiazepine receptor-specific agonist, had negligible effects on ex vivo binding of [3H]PK11195. We propose that the ex vivo receptor binding technique we used will facilitate determination of in vivo receptor occupancy of the peripheral benzodiazepine receptor.
authors.affiliation: Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd., Ohmiya, Saitama, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Funakoshi
authors.forename: S
authors.initials: S
authors.lastname: Chaki
authors.forename: S
authors.initials: S
authors.lastname: Okuyama
authors.forename: T
authors.initials: T
authors.lastname: Okubo
authors.forename: A
authors.initials: A
authors.lastname: Nakazato
authors.forename: M
authors.initials: M
authors.lastname: Nagamine
authors.forename: K
authors.initials: K
authors.lastname: Tomisawa
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D007546:Isoquinolines / Q000378:metabolism*; D008297:Male; D009830:Olfactory Bulb / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*; D014316:Tritium
chemical_list: D007546:Isoquinolines; D011963:Receptors, GABA-A; D014316:Tritium; C037850:PK 11195