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WAY-100635 is the first selective, silent 5-HT(1A) (5-hydroxytryptamine(1A), serotonin-1A) receptor antagonist. We have investigated the use of [ 3 H]WAY-100635 as a quantitative autoradiographic ligand in post-mortem human hippocampus, raphe and four cortical regions, and compared it with the 5-HT(1A) receptor agonist, [ 3 H]8-OH-DPAT. Saturation studies showed an average Kd for [ 3 H]WAY-100635 binding in hippocampus of 1.1 nM. The regional and laminar distributions of [ 3 H]WAY-100635 binding and [ 3 H]8-OH-DPAT binding were similar. The density of [ 3 H]WAY-100635 binding sites was 60-70% more than that of [ 3 H]8-OH-DPAT in all areas examined except the cingulate gyrus where it was 165% higher. [ 3 H]WAY-100635 binding was robust and was not affected by the post-mortem interval, freezer storage time or brain pH (agonal state). Using [ 3 H]WAY-100635, we confirmed an increase of 5-HT(1A) receptor binding sites in the frontal cortex in schizophrenia, previously demonstrated with [ 3 H]8-OH-DPAT. Compared to [ 3 H]8-OH-DPAT, [ 3 H]WAY-100635 has two advantages: it has a higher selectivity and affinity for the 5-HT(1A) receptor, and it recognizes 5-HT(1A) receptors whether or not they are coupled to a G-protein, whereas [ 3 H]8-OH-DPAT primarily detects coupled receptors. Given these considerations, the [ 3 H]WAY-100635 binding data in schizophrenia clarify two points. First, they indicate that the elevated [ 3 H]8-OH-DPAT binding seen in the same cases is attributable to an increase of 5-HT(1A) receptors rather than any other binding site. Second, the enhanced [ 3 H]8-OH-DPAT binding in schizophrenia reflects an increased density of 5-HT(1A) receptors, not an increased percentage of 5-HT(1A) receptors which are G-protein-coupled. We conclude that [ 3 H]WAY-100635 is a valuable autoradiographic ligand for the qualitative and quantitative study of 5-HT(1A) receptors in the human brain.

Original publication

DOI

10.1016/S0197-0186(96)00124-6

Type

Journal article

Journal

Neurochemistry International

Publication Date

07/06/1997

Volume

30

Pages

565 - 574