[H-3] ALNESPIRONE - A NOVEL SPECIFIC RADIOLIGAND OF 5-HT1A RECEPTORS IN THE RAT-BRAIN

Determination of the optimal assay conditions for the specific binding of a tritiated derivative of the novel potential anxiolytic drug alne spirone (S-20499, ropylamino]butyl-8-azaspiro(4,5)-decane-7,9-dione) a llowed the demonstration that this radioligand bound with a high affin ity (K-d = 0.36 nM) to a homogeneous class of sites in rat hippocampal membranes. The pharmacological properties of [H-3]alnespirone specifi c binding sites matched exactly (r = 0.95) those of 5-HT1A receptors i dentified with [H-3]8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) as radioligand. Furthermore, membrane binding experiments and autorad iographic labeling of tissue sections showed that the regional distrib ution of [H-3]alnespirone specific binding sites in the rat brain and spinal cord superimposed over that of 5-HT1A receptors specifically la beled by [H-3]8-OH-DPAT. However, the differential sensitivity of [H-3 ]alnespirone and [H-3]8-OH-DPAT specific binding to various physicoche mical effecters (temperature, pH, Mn2+, N-ethyl-maleimide) supports th e idea that these two agonist radioligands did not recognize 5-HT1A re ceptors exactly in the same way. These differences probably account fo r the reported inability of alnespirone, in contrast to 8-OH-DPAT, to induce some 5-HT1A receptor-mediated behavioural effects in rats. (C) 1997 Elsevier Science B.V.