Differential effects of systemically administered nor-binaltorphimine (nor-BNI) on kappa-opioid agonists in the mouse writhing assay

Psychopharmacology (Berl). 1994 Jul;115(3):311-9. doi: 10.1007/BF02245071.


The opioid antagonist effects of systemically administered nor-binaltorphimine (nor-BNI) were evaluated against the kappa agonists CI-977, U69,593, U50,488, ethylketocyclazocine (EKC), Mr2034 and bremazocine, the mu agonist morphine and the alkaloid delta agonist BW-373U86 in the acetic acid-induced writhing assay in mice. All eight agonists completely and dose-dependently inhibited writhing. Antagonism of CI-977 was apparent 1 h after administration of 32 mg/kg nor-BNI, peaking after 4 h and was maintained for at least 4 weeks; no antagonist effects of nor-BNI were apparent after 8 weeks. Nor-BNI (32 mg/kg) caused little or no antagonism of morphine or BW-373U86 at 1 h and none at 24 h after nor-BNI administration. Subsequently, dose-effect curves for CI-977, U50,488, U69,593, EKC, Mr2034 and bremazocine were determined 24 h after pretreatment with 3.2, 10 and 32 mg/kg nor-BNI. Pretreatment with 3.2 mg/kg nor-BNI produced significant antagonism of all six kappa agonists, suggesting that their antinociceptive effects were mediated at least in part by nor-BNI-sensitive kappa receptors. At higher doses, nor-BNI dose-dependently shifted the agonist dose-effect curves of CI-977, U50,488, U69,593 and bremazocine, but not those of EKC and Mr2034, suggesting that the latter compounds may be producing effects via nor-BNI-insensitive receptors. Mu receptor involvement was demonstrated following a 24 h pretreatment with 32 mg/kg beta-FNA in combination with nor-BNI, which significantly increased the degree of antagonism of Mr2034 and EKC from that seen with nor-BNI alone.2+ off

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Injections, Subcutaneous
  • Male
  • Mice
  • Naltrexone / analogs & derivatives*
  • Naltrexone / antagonists & inhibitors
  • Naltrexone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Pain Measurement / drug effects*
  • Receptors, Opioid, kappa / agonists*
  • Receptors, Opioid, kappa / antagonists & inhibitors
  • Receptors, Opioid, mu / antagonists & inhibitors


  • Narcotic Antagonists
  • Receptors, Opioid, kappa
  • Receptors, Opioid, mu
  • norbinaltorphimine
  • Naltrexone
  • beta-funaltrexamine