title: Probes for narcotic receptor mediated phenomena. 5. Narcotic antagonist irreversible ligands based on endoethenotetrahydrooripavine.
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: D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D005910:Glioma / Q000378:metabolism; D006822:Hybrid Cells / Q000378:metabolism; D008024:Ligands; D051379:Mice; D009019:Morphinans / Q000494:pharmacology*; D009447:Neuroblastoma / Q000378:metabolism; D051381:Rats; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D013797:Thebaine / Q000031:analogs & derivatives*
chemical_list: D008024:Ligands; D009019:Morphinans; D011957:Receptors, Opioid; D013797:Thebaine