Brain uptake and plasma metabolism of [C-11]vinpocetine: A preliminary PETstudy in a cynomolgus monkey

Vinpocetine, a vinca alkaloid, is a widely used therapeutic agent in patien ts with acute and chronic stroke. To reveal the mechanisms of vinpocetine a ction in the brain, vinpocetine was labeled with C-11. Positron emission to mography (PET) was used to determine the uptake and distribution of [C-11]v inpocetine in brain regions and the trunk of a cynomolgous monkey in two in dependent measurements. The concentration of vinpocetine and its labeled me tabolites was determined in blood and plasma using high-performance liquid chromatography (HPLC). Almost identical measurements were obtained in the t wo independent studies. After intravenous administration, following an init ial peak, the total concentration of radioactivity in blood was relatively stable with time, whereas the concentration of the unchanged compound decre ased with time in an exponential manner. The uptake of [C-11]vinpocetine in brain was rapid, and 5% of the radioactivity totally injected was present in the brain 2 minutes after drug administration, indicating that the compo und entered the brain readily. The radioactivity uptake was heterogeneously distributed among brain regions and was highest in the thalamus, the basal ganglia, and certain neocortical regions. The high brain uptake and the he terogeneous regional distribution indicate that direct central nervous syst em (CNS) effects of vinpocetine must be considered as explanation for the t herapeutic effects. The detailed exploration of this suggestion requires fu rther studies.