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

J Med Chem. 1996 Mar 1;39(5):1125-9. doi: 10.1021/jm950662c.

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.

Publication types

  • Comparative Study

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Animals
  • Behavior, Animal / drug effects
  • Buspirone / analogs & derivatives*
  • Buspirone / chemical synthesis
  • Buspirone / metabolism
  • Buspirone / pharmacology
  • Hippocampus / metabolism
  • Ligands
  • Male
  • Molecular Structure
  • Peptide Fragments / chemistry
  • Rats
  • Rats, Wistar
  • Receptors, Serotonin / metabolism*
  • Receptors, Serotonin, 5-HT1
  • Reserpine / pharmacology
  • Serotonin Receptor Agonists / chemical synthesis*
  • Serotonin Receptor Agonists / metabolism
  • Tetrahydroisoquinolines

Substances

  • 8-(4-(2-(1,2,3,4-tetrahydroisoquinolinyl))butyl)-8-azaspiro(4.5)decane-7,9-dione
  • Ligands
  • Peptide Fragments
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Serotonin Receptor Agonists
  • Tetrahydroisoquinolines
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Reserpine
  • Buspirone