Probes for narcotic receptor mediated phenomena. 5. Narcotic antagonist irreversible ligands based on endoethenotetrahydrooripavine

Life Sci. 1983:33 Suppl 1:159-62. doi: 10.1016/0024-3205(83)90468-x.

Abstract

Nine new compounds have been synthesized as potential affinity ligands for specific opioid receptors. The biochemical properties of three of these compounds were examined in detail and one of them, N-cyclopropylmethyl-7 alpha-methylfumaroylamido-6, 14-endoethenotetrahydronororipavine (NIH 10236), was found to be a potent irreversible ligand for the delta opioid receptor. It had the properties of a narcotic antagonist, as determined by its effect on adenylate cyclase activity of NG108-15 neuroblastoma-glioma cell homogenates. It is, thus, the first delta specific alkylating ligand known which is a narcotic antagonist. A second compound, the N-cyclopropylmethyl-7 alpha-isothiocyanato-6, 14-endoethenotetrahydronororipavine (NIH 10235) was found to be a mu specific alkylating ligand in brain and a reversible antagonist in the NG108-15 cells.

MeSH terms

  • Animals
  • Binding, Competitive
  • Brain / metabolism
  • Cell Line
  • Cell Membrane / metabolism
  • Glioma / metabolism
  • Hybrid Cells / metabolism
  • Ligands
  • Mice
  • Morphinans / pharmacology*
  • Neuroblastoma / metabolism
  • Rats
  • Receptors, Opioid / drug effects
  • Receptors, Opioid / metabolism*
  • Thebaine / analogs & derivatives*

Substances

  • Ligands
  • Morphinans
  • Receptors, Opioid
  • Thebaine