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 function...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1996-03, Vol.39 (5), p.1125-1129
Main Authors: Mokrosz, Jerzy L, Dereń-Wesołek, Anna, Tatarczyńska, Ewa, Duszyńska, Beata, Bojarski, Andrzej J, Mokrosz, Maria J, Chojnacka-Wójcik, Ewa
Format: Article
Language:English
Subjects:
8-Hydroxy-2-(di-n-propylamino)tetralin - pharmacology
Animals
Behavior, Animal - drug effects
Biological and medical sciences
Buspirone - analogs & derivatives
Buspirone - chemical synthesis
Buspirone - metabolism
Buspirone - pharmacology
Hippocampus - metabolism
Ligands
Male
Medical sciences
Molecular Structure
Neuropharmacology
Neurotransmitters. Neurotransmission. Receptors
Peptide Fragments - chemistry
Pharmacology. Drug treatments
Rats
Rats, Wistar
Receptors, Serotonin - metabolism
Receptors, Serotonin, 5-HT1
Reserpine - pharmacology
Serotonin Receptor Agonists - chemical synthesis
Serotonin Receptor Agonists - metabolism
Serotoninergic system
Tetrahydroisoquinolines
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Summary: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.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm950662c