Brain Uptake and Plasma Metabolism of [¹¹C]Vinpocetine: A Preliminary PET Study in a Cynomolgus Monkey

Abstract

Vinpocetine, a vinca alkaloid, is a widely used therapeutic agent in patients with acute and chronic stroke. To reveal the mechanisms of vinpocetine action in the brain, vinpocetine was labeled with 11C. Positron emission tomography (PET) was used to determine the uptake and distribution of [11C]vinpocetine in brain regions and the trunk of a cynomolgous monkey in two independent measurements. The concentration of vinpocetine and its labeled metabolites was determined in blood and plasma using high-performance liquid chromatography (HPLC). Almost identical measurements were obtained in the two independent studies. After intravenous administration, following an initial peak, the total concentration of radioactivity in blood was relatively stable with time, whereas the concentration of the unchanged compound decreased with time in an exponential manner. The uptake of [11C]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 compound 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 heterogeneous regional distribution indicate that direct central nervous system (CNS) effects of vinpocetine must be considered as explanation for the therapeutic effects. The detailed exploration of this suggestion requires further studies.

Drug distribution in man: a positron emission tomography study after oral administration of the labelled neuroprotective drug vinpocetine

“…In recent PET studies with carbon-11 labelled vinpocetine in monkeys and healthy young male volunteers, we have confirmed that vinpocetine passes the blood-brain barrier readily and enters the brain in a relatively large fraction [6,7]. In healthy men on average 3.7% of the total injected dose was in the brain shortly after i.v.…”

Antioxidant strategies for Alzheimer's disease

“…once favoured as a treatment for stroke (Bereczki & Fekete, 1999;Gulyas et al 1999), owing to its effects on cerebral blood flow and glucose utilization following ischaemia (Rischke & Krieglstein, 1990). Vinpocetine has also been shown to be a free radical scavenger and to protect PC 12 cells from P-amyloid toxicity.…”

Vinpocetine Is a Potent Blocker of Rat NaV1.8 Tetrodotoxin-Resistant Sodium Channels

“…However, the drug as a very high volume of distribution and readily partitions into the brain (Gulyas et al, 1999) and, presumably, other fatty tissues that are likely to include the peripheral nerves. Hence, true tissue exposure levels may be somewhat higher than the circulating plasma level and, in any event, are within the range that might be expected to produce some attenuation of sodium channel function.…”