8-[4-[2-(1,2,3,4-tetrahydroisoquinolinyl)]butyl]-8-azaspiro[4,5]decane-7,9-dione: A new 5-HT1A receptor ligand with the same activity profile as buspirone

A new analog of buspirone (1), i.e., 8-[4-[2-(1,2,3,4-tetrahydroisoquinolinyl)]butyl]8-azaspiro[4.5] decane-7,9-dione (6a), was synthesized. In was demonstrated that buspirone and its analog 6a were equipotent 5-HT1A ligands. Several behavioral models showed that 6a had essentially the same functional profile at 5-HT1A receptors as buspirone. The obtained results permit a conclusion that the basic nitrogen atom and terminal, bulky cycloimide moiety, but not the 2-pyrimidinyl group, of buspirone are directly involved in the formation of the bioactive complex with 5-HT1A receptors.