ANTAGONISTIC MODULATION BETWEEN THE DELTA-OPIOID AGONIST BW373U86 ANDTHE MU-OPIOID AGONIST FENTANYL IN MICE

This study was performed to assess the interactions that occur between delta-and mu opioid receptors by studying effects of the systemically active nonpeptide delta agonist BW373U86 and the mu agonist fentanyl in mice. Concentrations of the compounds were varied, and analgesic re sponses were determined by 55 degrees C hot-plate assays. BW373U86 pro duced hotplate antinociceptive activity along with convulsive side eff ects. These effects could be antagonized by the selective delta antago nist naltrindole. Fentanyl produced hot-plate antinociceptive activity with Straub tail and hyperactivity as side effects. When BW373U86 and fentanyl were coadministered, BW373U86 convulsive activity was attenu ated by fentanyl in a dose-dependent manner and the fentanyl-induced S traub tail effect was antagonized by BW373U86, also in a dose-dependen t manner. Hot-plate analgesic activity was additive between the two co mpounds. The delta antagonist naltrindole partially antagonized the ab ility of BW373U86 to block the fentanyl-induced Straub tail effect. Th e mu antagonist beta- funaltrexamine antagonized the fentanyl-induced blockade of the convulsive effects of BW373U86. These data suggest tha t complex inhibitory interactions take place between mu and delta rece ptors in mice. Future studies are clearly needed to study the neuromod utatory effects of mu and delta receptors. The widespread use of mu ag onists in the clinic indicates that a large number of patients exist w ho could greatly benefit from the conjunctive use of delta pharmaceuti cals.