Comparative binding of μ and δ selective ligands in whole brain and pons/medulla homogenates from rat: Affinity profiles of fentanyl derivatives

Abstract

The comparative binding characteristics of the μ opioid receptor selective ligand [ 3H]-[ d-Ala 2-MePhe 4-glyol 5]enkephalin ([ 3H]-DAGO) and of the δ receptor ligand [ 3H]-[ d-Pen 2, d-Pen 5]enkephalin([ 3H]-DPDPE) have been studied in homogenates of both whole brain and of pons/medulla regions from the rat. The receptor affinities of five 4-anilinopiperidine drugs (fentanyl derivatives) and of morphine have been determined by inhibition studies, using [ 3H]-DAGO and [ 3H]-DPDPE as markers of the μ and δ opioid binding sites, respectively. The concentration of δ opioid sites in pons/medulla was found to be approximately one third that of μ sites. The concentrations of both μ and δ sites in whole brain were similar to that of μ sites in pons/medulla. The rank order of affinities of the unlabelled drugs was dissimilar at the μ and δ sites. The most potent fentanyl derivatives exhibited negligible preference for the μ or δ sites, in contrast to the least potent compound, alfentanil which showed an extremely high μ-site selectivity.