Reversal by beta-funaltrexamine of the antinociceptive effect of opioid agonists in the rat

Br J Pharmacol. 1986 Aug;88(4):867-72. doi: 10.1111/j.1476-5381.1986.tb16260.x.

Abstract

The effect of the irreversible opioid receptor antagonist, beta-funaltrexamine (beta-FNA), on antinociception produced by mu- and kappa-receptor agonists was studied in the rat. beta-FNA, 20 to 80 mg kg-1, s.c., given 24 h before testing, produced a dose-related antagonism of the effects of morphine in the paw pressure, hotplate and tail-flick tests. Following the 80 mg kg-1 dose, the degree of antagonism of morphine was stable for up to 48 h after dosing, but was reduced by 5 days and had disappeared by 8 days. In the paw pressure test, beta-FNA, 40 mg kg-1, s.c., antagonized the effects of fentanyl, buprenorphine, tifluadom, ethylketocyclazocine and proxorphan; it was without effect against the highly selective kappa-agonist, U-50,488. In light of these results, the possible opioid receptor selectivities of both the agonists and beta-FNA are reassessed.

MeSH terms

  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
  • Animals
  • Benzodiazepines / antagonists & inhibitors
  • Buprenorphine / antagonists & inhibitors
  • Cyclazocine / analogs & derivatives
  • Cyclazocine / antagonists & inhibitors
  • Ethylketocyclazocine
  • Fentanyl / antagonists & inhibitors
  • Male
  • Naltrexone / analogs & derivatives*
  • Naltrexone / pharmacology
  • Pain*
  • Pyrrolidines / pharmacology
  • Rats
  • Receptors, Opioid / metabolism
  • Receptors, Opioid, kappa
  • Receptors, Opioid, mu

Substances

  • Pyrrolidines
  • Receptors, Opioid
  • Receptors, Opioid, kappa
  • Receptors, Opioid, mu
  • Benzodiazepines
  • Buprenorphine
  • Ethylketocyclazocine
  • Naltrexone
  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
  • beta-funaltrexamine
  • Cyclazocine
  • tifluadom
  • Fentanyl