PET NEUROIMAGING WITH [C-11] VENLAFAXINE - SEROTONIN UPTAKE INHIBITION, BIODISTRIBUTION AND BINDING IN LIVING PIG BRAIN

The brain binding kinetics and distribution of the antidepressant venl afaxine, labelled with C-11 in the O-methyl position, was studied by P ET after intravenous injection in anesthetized pigs. In addition, venl afaxine's action on serotonin (5-HT) uptake was studied in vitro in bl ood platelets obtain from humans or pigs. Venlafaxine resembled imipra mine, paroxetine and citalopram in causing a dose-dependent inhibition of 5-HT uptake in blood platelets from pigs and humans. Venlafaxine-d erived radioactivity entered the living brain readily and showed highe r binding potentials in diencephalic and telencephalic regions than in cerebellum Acute administration of an antidepressant drug (i.e. imipr amine, citalopram or paroxetine) enhanced the distribution and altered the binding of venlafaxine in certain brain regions. The findings sho w that [C-11]venlafaxine is not an ideal PET radiotracer mainly becaus e of its relatively low binding potentials and its lack of specificity for the 5-HT transporter in living brain. (C) 1997 Elsevier Science B .V.