[11C]vinpocetine: a prospective peripheral benzodiazepine receptor ligand for primate PET studies.
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.
Gulyás
Balázs
B
Karolinska Institute, Psychiatry Section, Department of Clinical Neuroscience, Karolinska Hospital, S-17176 Stockholm, Sweden. balazs.gulyas@neuro.ki.se
Halldin
Christer
C
Vas
Adám
A
Banati
Richard B
RB
Shchukin
Evgeny
E
Finnema
Sjoerd
S
Tarkainen
Jari
J
Tihanyi
Károly
K
Szilágyi
Géza
G
Farde
Lars
L
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*
D008024:Ligands; D019275:Radiopharmaceuticals; D011963:Receptors, GABA-A; D014748:Vinca Alkaloids; C013983:vinpocetine