title: Photoaffinity probes for opiate receptors: synthesis and properties of a nitro-azido-derivative of 14-beta-aminomorphinone.
abstract: The potential photoaffinity ligand 14-beta-(o-nitro, p-azido)-cinnamoyl-amino-N-cyclopropylmethylnormorphinone (NAM) and its derivative NOM, lacking the p-azido function, were synthesised and their opiate receptor activity determined in isolated tissue preparations. The ligands showed slow receptor kinetics. NAM was a pure competitive antagonist of met5-enkephalin responses in MVD while its antagonism of normorphine responses in GPI appeared non-competitive and non-reversible. In radioligand binding assays NOM completely and irreversibly blocked specific binding of 3H-DHM. Partial blockade of 3H-DADL specific binding was reversible by washing. No binding of NOM to kappa sites was observed. The slow receptor kinetics of NAM preclude its use as a photoaffinity ligand but suggest that a chemically more stable derivative may have a role as a pseudocovalent blocker of mu-receptors.
mesh_terms: D000345:Affinity Labels / Q000138:chemical synthesis*; D000818:Animals; D001386:Azides / Q000138:chemical synthesis* / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D007700:Kinetics; D009022:Morphine Derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011957:Receptors, Opioid / Q000378:metabolism*
chemical_list: C040241:14 beta-(2-nitro-4-azido)cinnamoylamino-N-cyclopropylmethylnormorphinone; D000345:Affinity Labels; D001386:Azides; D009022:Morphine Derivatives; D011957:Receptors, Opioid