[H-3] SUMATRIPTAN BINDING-SITES IN HUMAN BRAIN - REGIONAL-DEPENDENT LABELING OF 5-HT1D AND 5-HT1F RECEPTORS

The general properties of [H-3]sumatriptan binding sites in postmortem human brain tissue sections are described. High concentrations of aut oradiographic grains were seen in globus pallidus = substantia nigra > cortex > putamen > hippocampus. While 5-HT (5-hydroxytryptamine) disp laced in all regions more than 90% of [H-3]sumatriptan binding, the le vel of binding inhibited by 5-CT (5-carboxamidotryptamine) varied in e ach region. Although the binding inhibited by 5-CT in some regions suc h as globus pallidus and substantia nigra was equivalent to that obtai ned with 5-HT, in cortical areas, such as frontal cortex and hippocamp us, a substantial level of binding insensitive to 5-CT was seen. In ad dition, in membrane binding assays, 10 nM metergoline displaced most [ H-3]sumatriptan specific binding in striatum and only 16% in frontal c ortex. In the human brain sumatriptan binds to at least two 5-HT1 rece ptors, 5-HT1D and 5-HT1F.