title: [11C]vinpocetine: a prospective peripheral benzodiazepine receptor ligand for primate PET studies.
abstract: Vinpocetine, a synthetic derivative of the Vinca minor alkaloid vincamine, is a widely used drug in neurological practice. We tested the hypothesis that vinpocetine binds to peripheral benzodiazepine binding sites (PBBS) and is therefore a potential ligand of PBBS. Positron emission tomography (PET) measurements in two cynomolgous monkeys showed that pretreatment with vinpocetine markedly reduced the brain uptake of [11C]PK11195, a known PBBS radioligand. On the other hand, whereas pretreatment with PK11195 increased the brain uptake of [11C]vinpocetine due to the blockade of PBBS in the periphery, it significantly reduced the binding potential (BP) values of [11C]vinpocetine in the whole brain and in individual brain structures to PK11195. These findings indicate that, whereas the two ligands have different affinities to PBBS, vinpocetine is a potent ligand of PBBS, which in turn suggests that the pharmacological activity of vinpocetine may involve the regulation of glial functions.
authors.affiliation: Karolinska Institute, Psychiatry Section, Department of Clinical Neuroscience, Karolinska Hospital, S-17176 Stockholm, Sweden. balazs.gulyas@neuro.ki.se
authors.forename: Balázs
authors.initials: B
authors.lastname: Gulyás
authors.forename: Christer
authors.initials: C
authors.lastname: Halldin
authors.forename: Adám
authors.initials: A
authors.lastname: Vas
authors.forename: Richard B
authors.initials: RB
authors.lastname: Banati
authors.forename: Evgeny
authors.initials: E
authors.lastname: Shchukin
authors.forename: Sjoerd
authors.initials: S
authors.lastname: Finnema
authors.forename: Jari
authors.initials: J
authors.lastname: Tarkainen
authors.forename: Károly
authors.initials: K
authors.lastname: Tihanyi
authors.forename: Géza
authors.initials: G
authors.lastname: Szilágyi
authors.forename: Lars
authors.initials: L
authors.lastname: Farde
mesh_terms: D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D001923:Brain Chemistry; D005260:Female; D007091:Image Processing, Computer-Assisted; D008024:Ligands; D008252:Macaca fascicularis; D008279:Magnetic Resonance Imaging; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000187:drug effects*; D014748:Vinca Alkaloids / Q000494:pharmacology*
chemical_list: D008024:Ligands; D019275:Radiopharmaceuticals; D011963:Receptors, GABA-A; D014748:Vinca Alkaloids; C013983:vinpocetine