ANALGESIA PRODUCED BY E-2078, A SYSTEMICALLY ACTIVE DYNORPHIN ANALOG, IN MICE

  • 1 March 1990
    • journal article
    • research article
    • Vol. 252  (3) , 1247-1254
Abstract
E-2078 is a very stable dynorphin analog that has the same affinity and selectivity for opioid receptors as dynorphin-A by in vitro bioassay. In the present study, we have characterized the receptor selectivity of E-2078 in .mu.-, .delta.- and .kappa.-representative binding assays, and have evaluated the analgesic effect of systemically administered E-2078 by the tail pinch, tail flick and formalin tests in mice. E-2078 possessed a higher affinity for .kappa.-receptors than for .mu.- or .delta.-receptors in the receptor-binding assay. Dose-related, long-lasting analgesia was produced by s.c. injection of E-2078, and its peak effect was observed 2 hr after s.c. administration in all the analgesic tests. This analgesic effect was produced at doses that did not affect rotarod latency. Post-treatment with naloxone dose-dependently reversed the analgesic effects of both E-2078 and morphine, but E-2078-induced analgesia was relatively resistant to naloxone antagonism. Pretreatment with the .kappa.-antagonist, nor-binaltorphimine, antagonized the analgesic effect of E-2078 but had little effect on the analgesic action of morphine. These data indicate that E-2078 is a systemically active analgesic and suggest that the activation of .kappa.-opioid receptors contributes to analgesia.