Photoaffinity probes for opiate receptors: Synthesis and properties of a nitro-azido-derivative of 14-β-aminomorphinone

The potential photoaffinity ligand 14-β-( 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 met 5-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 3-H-DHM. Partial blockade of 3H-DADL specific binding was reversible by washing. No binding of NOM to ▪ 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 μ-receptors.