title: 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.
abstract: 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-HT(1A) ligands. Several behavioral models showed that 6a had essentially the same functional profile at 5-HT(1A) 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.
authors.affiliation: Department of Medicinal Chemistry, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
authors.forename: J L
authors.initials: JL
authors.lastname: Mokrosz
authors.forename: A
authors.initials: A
authors.lastname: Dereń-Wesołek
authors.forename: E
authors.initials: E
authors.lastname: Tatarczyńska
authors.forename: B
authors.initials: B
authors.lastname: Duszyńska
authors.forename: A J
authors.initials: AJ
authors.lastname: Bojarski
authors.forename: M J
authors.initials: MJ
authors.lastname: Mokrosz
authors.forename: E
authors.initials: E
authors.lastname: Chojnacka-Wójcik
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002065:Buspirone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism; D008024:Ligands; D008297:Male; D015394:Molecular Structure; D010446:Peptide Fragments / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D012110:Reserpine / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000138:chemical synthesis* / Q000378:metabolism; D044005:Tetrahydroisoquinolines
chemical_list: C098652:8-(4-(2-(1,2,3,4-tetrahydroisoquinolinyl))butyl)-8-azaspiro(4.5)decane-7,9-dione; D008024:Ligands; D010446:Peptide Fragments; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D044005:Tetrahydroisoquinolines; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D012110:Reserpine; D002065:Buspirone