Kappa-receptor selective binding of opioid ligands with a heterocyclic bicyclo[3.3.1]nonan-9-one structure

S. Benyhe, Á Márki, Corina Nachtsheim, Ulrike Holzgrabe, Anna Borsodi

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Previous pharmacological results have suggested that members of the heterocyclic bicyclo[3.3.1]nonan-9-one-like compounds are potent κ-opioid receptor specific agonists. One lead molecule of this series, called compound 1 (dimethyl 7-methyl-2,4-di-2-pyridyl-3,7-diazabicyclo[3.3.1]nonan-9-one-1,5-dicarboxylate) exhibited high affinity for [3H]ethylketocyclazocine and [ 3H]U-69,593 binding sites in guinea pig cerebellar membranes which known to be a good source for κ1, receptors. It was shown by molecular modelling that heterocyclic bicyclo[3.3.1]nonan-9-ones fit very well with the structure of ketazocine, a prototypic κ-selective benzomorphan compound; when compared to the arylacetamide structure of U-69,593, a specific κ1-receptor agonist, a similar geometry was found with a slightly different distribution of the charges. It is postulated, that the essential structural skeleton involved in the opioid activity is an aryl-propyl-amine element distributed along the N7-C6-C5-C4-aryl bonds.

Original languageEnglish
Pages (from-to)147-155
Number of pages9
JournalActa biologica Hungarica
Volume54
Issue number2
DOIs
Publication statusPublished - Sep 23 2003

Keywords

  • Guinea pig cerebellum
  • Opioid receptors
  • Radioligand binding
  • κ-opioids

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Environmental Science(all)
  • Neurology

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