PET studies on the brain uptake and regional distribution of [11C]vinpocetine in human subjects

• Published in: Acta neurologica Scandinavica Vol. 106; no. 6; pp. 325 - 332
• Main Authors: Gulyás, B., Halldin, C., Sandell, J., Karlsson, P., Sóvágó, J., Kárpáti, E., Kiss, B., Vas, Á., Cselényi, Z., Farde, L.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Munksgaard International Publishers 01.12.2002; Blackwell
• Subjects: Adult; Biological and medical sciences; Blood-Brain Barrier - drug effects; Brain - anatomy & histology; Brain - diagnostic imaging; Brain - drug effects; Carbon Radioisotopes - blood; Cardiovascular system; Cerebrovascular Circulation - drug effects; Chromatography, High Pressure Liquid; drug distribution; human brain; Humans; Magnetic Resonance Imaging; Male; Medical sciences; Neuroprotective Agents - blood; Neuroprotective Agents - pharmacokinetics; PET; Pharmacology. Drug treatments; Reference Values; Time Factors; Tomography, Emission-Computed; Vasodilator agents. Cerebral vasodilators; Vinca Alkaloids - blood; Vinca Alkaloids - pharmacokinetics; vinpocetine; Radionuclide study; Human; Vasodilator agent; Radiolabelling; Antimigrainous agent; Central nervous system; Male; Single photon emission tomography; Vinpocetine; Alkaloid; human brain; Distribution; drug distribution; Adult; Mechanism of action; Pharmacokinetics; PET; Brain (vertebrata)
• ISSN: 0001-6314; 1600-0404
• DOI: 10.1034/j.1600-0404.2002.01302.x

Gulyás B, Halldin C, Sandell J, Karlsson P, Sóvágó J, Kárpáti E, Kiss B, Vas Á, Cselényi Z, Farde L. PET studies on the brain uptake and regional distribution of [11C]vinpocetine in human subjects. Acta Neurol Scand 2002: 106: 325–332. © Blackwell Munksgaard 2002. Objectives– Vinpocetine is a compound widely used in the prevention and treatment of cerebrovascular diseases. It is still not clear whether the drug has a direct and specific effect on neurotransmission or its effects are due to extracerebral actions, such as changes in cerebral blood flow. The main objective of the present investigation was to determine the global uptake and regional distribution of radiolabelled vinpocetine in the human brain in order to explore whether it may have direct central nervous system effects. Material and methods– Three healthy subjects were examined with positron emission tomography and [11C]vinpocetine. The regional uptake was determined in anatomically defined volumes‐of‐interest. The fractions of [11C]vinpocetine and labelled metabolites in plasma were determined using high pressure liquid chromatography. Results– The uptake of [11C]vinpocetine in brain was rapid and 3.7% (mean; n=4) of the total radioactivity injected was in brain 2 min after radioligand administration. The uptake was heterogeneously distributed among brain regions. When compared with the cerebellum, an a priori reference region, the highest regional uptake was in the thalamus, upper brain stem, striatum and cortex. 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. Conclusion– Vinpocetine, administered intravenously in humans, readily passes the blood–brain barrier and enters the brain. Its regional uptake and distribution in the brain is heterogeneous, indicating binding to specific sites. The brain regions showing increased uptake in the human brain correspond to those in which vinpocetine has been shown to induce elevated metabolism and blood flow. These observations support the hypothesis that vinpocetine has direct neuronal actions in the human brain.