d-Propoxyphene acts differently from morphine on opioid receptor-effector mechanisms

The actions of d-propoxyphene and morphine on opioid receptor mechanisms were compared. In assay measuring receptor binding selectivity in vitro, with dihydromorphine, naloxone and an enkephalin analogue as radioactive ligands, d-propoxyphene differed from morphine in having a higher relative affinity for sites occupied by the peptide. Naloxone was more potent in antagonizing morphine- than d-propoxyphene-induced antinociception in the mouse hot-plate test. In morphine-tolerant mice showing three-fold lower morphine sensitivity the antinociceptive efficacy of d-propoxyphene was unchanged. The results indicate differences in receptor-effector mechanisms between d-propoxyphene and morphine.