title: [Cerebral uptake and metabolism of (11C) Vinpocetine in monkeys: PET studies].
abstract: Vinpocetine, a vinca alkaloid, is a therapeutic agent widely used in the treatment of acute and chronic stroke patients. To explore the uptake and distribution of vinpocetine in the primate brain, vinpocetine was labelled with 11C and positron emission tomography (PET) was used to measure the uptake and distribution of 11C-vinpocetine in the brain and the trunk of a cynomolgous monkey. HPLC was used to determine the concentration of vinpocetine and its labelled metabolites in blood and plasma. Following the radioligand's intravenous administration, after an initial peak, the total concentration of radioactivity in blood was relatively stable with time. The uptake of 11C-vinpocetine into the brain was rapid and about 5% of the total injected radioactivity was present in the brain two minutes after drug administration. These facts indicate that the compound passes the blood-brain barrier readily and enters the brain. The radioactivity uptake was heterogeneously distributed among brain regions. The highest concentrations were found in the thalamus, the basal ganglia and certain neocortical regions. In an earlier PET investigation on chronic stroke patients the highest increases in cerebral blood flow and glucose metabolism after intravenous vinpocetine treatment occurred in these anatomical structures. The heterogenous regional distribution of vinpocetine and the observation that the highest uptake values in brain structures go parallel with the greatest regional blood flow and glucose metabolic rate increases indicate that direct CNS effects of vinpocetine should be considered as an explanation for the therapeutic effects. The confirmation of this suggestion requires further investigations.
authors.affiliation: Karolinska Institutet, Department of Neuroscience, Stockholm.
authors.forename: B
authors.initials: B
authors.lastname: Gulyás
authors.forename: C
authors.initials: C
authors.lastname: Halldin
authors.forename: P
authors.initials: P
authors.lastname: Karlsson
authors.forename: Y H
authors.initials: YH
authors.lastname: Chou
authors.forename: C G
authors.initials: CG
authors.lastname: Swahn
authors.forename: P
authors.initials: P
authors.lastname: Bönöczk
authors.forename: L
authors.initials: L
authors.lastname: Farde
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects; D002561:Cerebrovascular Disorders / Q000188:drug therapy / Q000517:prevention & control*; D004195:Disease Models, Animal; D006801:Humans; D007275:Injections, Intravenous; D008252:Macaca fascicularis; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D011869:Radioligand Assay; D014055:Tomography, Emission-Computed; D014748:Vinca Alkaloids / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D010975:Platelet Aggregation Inhibitors; D014748:Vinca Alkaloids; C013983:vinpocetine