Opiate receptor binding affected differentially by opiates and opioid peptides

The potencies of various opiates in displacing several ³H-opiates ligands′ binding to rat brain membranes vary depending on the nature of the ligand. Whereas opiate antagonists, as well as the opioid peptides and somes agonists (etorphine, levorphanol and phenazocine) display similar affinities in displacing either ³H-opiate or ³H-methionine enkephalin binding, other agonists (such as morphine and oxymorphone) are considerably (20-50 times) weaker in displacing ³H-enkephalin than ³H-dihydromorphine binding. These agonists also compete for ³H-enkephalin binding with shallow displacement curves, and are greatly weakened in displacing ³H-naloxone binding in the presence of sodium. These agonists differ from the other opiate classes by processing a relatively hydrophilic component in their C-ring moieties which may provide a basis for the differential interactions of drugs with the opiate receptor.