Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

WAY-100635 is the first selective, silent 5-HT(1A) (5-hydroxytryptamine(1A), serotonin-1A) receptor antagonist. We have investigated the use of [3H]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, [3H]8-OH-DPAT. Saturation studies showed an average Kd for [3H]WAY-100635 binding in hippocampus of 1.1 nM. The regional and laminar distributions of [3H]WAY-100635 binding and [3H]8-OH-DPAT binding were similar. The density of [3H]WAY-100635 binding sites was 60-70% more than that of [3H]8-OH-DPAT in all areas examined except the cingulate gyrus where it was 165% higher. [3H]WAY-100635 binding was robust and was not affected by the post-mortem interval, freezer storage time or brain pH (agonal state). Using [3H]WAY-100635, we confirmed an increase of 5-HT(1A) receptor binding sites in the frontal cortex in schizophrenia, previously demonstrated with [3H]8-OH-DPAT. Compared to [3H]8-OH-DPAT, [3H]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 [3H]8-OH-DPAT primarily detects coupled receptors. Given these considerations, the [3H]WAY-100635 binding data in schizophrenia clarify two points. First, they indicate that the elevated [3H]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 [3H]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 [3H]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