Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1986 Aug;88(4):867–872. doi: 10.1111/j.1476-5381.1986.tb16260.x

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

A G Hayes, M Skingle, M B Tyers
PMCID: PMC1917077  PMID: 3017495

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.

Full text

PDF
872

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Carroll J. A., Miller L., Shaw J. S., Downes C. P. Mu-receptor binding in physiological media: comparison with isolated tissue data. Neuropeptides. 1984 Dec;5(1-3):89–92. doi: 10.1016/0143-4179(84)90034-9. [DOI] [PubMed] [Google Scholar]
  2. Chaillet P., Coulaud A., Zajac J. M., Fournie-Zaluski M. C., Costentin J., Roques B. P. The mu rather than the delta subtype of opioid receptors appears to be involved in enkephalin-induced analgesia. Eur J Pharmacol. 1984 May 18;101(1-2):83–90. doi: 10.1016/0014-2999(84)90033-5. [DOI] [PubMed] [Google Scholar]
  3. Corbett A. D., Kostelitz H. W., McKnight A. T., Paterson S. J., Robson L. E. Pre-incubation of guinea-pig myenteric plexus with beta-funaltrexamine: discrepancy between binding assays and bioassays. Br J Pharmacol. 1985 Jul;85(3):665–673. doi: 10.1111/j.1476-5381.1985.tb10562.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cowan A., Doxey J. C., Harry E. J. The animal pharmacology of buprenorphine, an oripavine analgesic agent. Br J Pharmacol. 1977 Aug;60(4):547–554. doi: 10.1111/j.1476-5381.1977.tb07533.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Galligan J. J., Mosberg H. I., Hurst R., Hruby V. J., Burks T. F. Cerebral delta opioid receptors mediate analgesia but not the intestinal motility effects of intracerebroventricularly administered opioids. J Pharmacol Exp Ther. 1984 Jun;229(3):641–648. [PubMed] [Google Scholar]
  6. Garzón J., Sánchez-Blázquez P., Lee N. M. [3H]Ethylketocyclazocine binding to mouse brain membranes: evidence for a kappa opioid receptor type. J Pharmacol Exp Ther. 1984 Oct;231(1):33–37. [PubMed] [Google Scholar]
  7. Gillan M. G., Kosterlitz H. W. Spectrum of the mu, delta- and kappa-binding sites in homogenates of rat brain. Br J Pharmacol. 1982 Nov;77(3):461–469. doi: 10.1111/j.1476-5381.1982.tb09319.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Goldstein A., James I. F. Site-directed alkylation of multiple opioid receptors. II. Pharmacological selectivity. Mol Pharmacol. 1984 May;25(3):343–348. [PubMed] [Google Scholar]
  9. Hayes A. G., Sheehan M. J., Tyers M. B. Determination of the receptor selectivity of opioid agonists in the guinea-pig ileum and mouse vas deferens by use of beta-funaltrexamine. Br J Pharmacol. 1985 Dec;86(4):899–904. doi: 10.1111/j.1476-5381.1985.tb11112.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hayes A., Kelly A. Profile of activity of kappa receptor agonists in the rabbit vas deferens. Eur J Pharmacol. 1985 Apr 16;110(3):317–322. doi: 10.1016/0014-2999(85)90558-8. [DOI] [PubMed] [Google Scholar]
  11. Huidobro F. Antidiuretic effect of morphine in the rat: tolerance and physical dependence. Br J Pharmacol. 1978 Oct;64(2):167–171. doi: 10.1111/j.1476-5381.1978.tb17286.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. James I. F., Goldstein A. Site-directed alkylation of multiple opioid receptors. I. Binding selectivity. Mol Pharmacol. 1984 May;25(3):337–342. [PubMed] [Google Scholar]
  13. Kosterlitz H. W., Paterson S. J., Robson L. E. Characterization of the kappa-subtype of the opiate receptor in the guinea-pig brain. Br J Pharmacol. 1981 Aug;73(4):939–949. doi: 10.1111/j.1476-5381.1981.tb08749.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Leander J. D. A kappa opioid effect: increased urination in the rat. J Pharmacol Exp Ther. 1983 Jan;224(1):89–94. [PubMed] [Google Scholar]
  15. Leander J. D. Further study of kappa opioids on increased urination. J Pharmacol Exp Ther. 1983 Oct;227(1):35–41. [PubMed] [Google Scholar]
  16. Lord J. A., Waterfield A. A., Hughes J., Kosterlitz H. W. Endogenous opioid peptides: multiple agonists and receptors. Nature. 1977 Jun 9;267(5611):495–499. doi: 10.1038/267495a0. [DOI] [PubMed] [Google Scholar]
  17. Rance M. J. Animal and molecular pharmacology of mixed agonist-antagonist analgesic drugs. Br J Clin Pharmacol. 1979;7 (Suppl 3):281S–286S. doi: 10.1111/j.1365-2125.1979.tb04701.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Rónai A. Z., Berzétei I. P., Székely J. I., Miglécz E., Kurgyis J., Bajusz S. Enkephalin-like character and analgesia. Eur J Pharmacol. 1981 Jan 29;69(3):263–271. doi: 10.1016/0014-2999(81)90472-6. [DOI] [PubMed] [Google Scholar]
  19. Sawynok J., Pinsky C., LaBella F. S. On the specificity of naloxone as an opiate antagonist. Life Sci. 1979 Nov 5;25(19):1621–1632. doi: 10.1016/0024-3205(79)90403-x. [DOI] [PubMed] [Google Scholar]
  20. Skingle M., Hayes A. G., Tyers M. B. Effects of opiates on urine output in the water-loaded rat and reversal by beta-funaltrexamine. Neuropeptides. 1985 Feb;5(4-6):433–436. doi: 10.1016/0143-4179(85)90047-2. [DOI] [PubMed] [Google Scholar]
  21. Tyers M. B. A classification of opiate receptors that mediate antinociception in animals. Br J Pharmacol. 1980 Jul;69(3):503–512. doi: 10.1111/j.1476-5381.1980.tb07041.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Tyers M. B. Studies on the antinociceptive activities of mixtures of mu- and kappa-opiate receptor agonists and antagonists. Life Sci. 1982 Sep 20;31(12-13):1233–1236. doi: 10.1016/0024-3205(82)90350-2. [DOI] [PubMed] [Google Scholar]
  23. Upton N., Sewell R. D., Spencer P. S. Analgesic actions of mu- and kappa-opiate agonists in rats. Arch Int Pharmacodyn Ther. 1983 Apr;262(2):199–207. [PubMed] [Google Scholar]
  24. Villiger J. W. Binding of buprenorphine to opiate receptors. Regulation by guanyl nucleotides and metal ions. Neuropharmacology. 1984 Mar;23(3):373–375. doi: 10.1016/0028-3908(84)90201-6. [DOI] [PubMed] [Google Scholar]
  25. Vonvoigtlander P. F., Lahti R. A., Ludens J. H. U-50,488: a selective and structurally novel non-Mu (kappa) opioid agonist. J Pharmacol Exp Ther. 1983 Jan;224(1):7–12. [PubMed] [Google Scholar]
  26. Ward S. J., Portoghese P. S., Takemori A. E. Pharmacological characterization in vivo of the novel opiate, beta-funaltrexamine. J Pharmacol Exp Ther. 1982 Mar;220(3):494–498. [PubMed] [Google Scholar]
  27. Ward S. J., Portoghese P. S., Takemori A. E. Pharmacological profiles of beta-funaltrexamine (beta-FNA) and beta-chlornaltrexamine (beta-CNA) on the mouse vas deferens preparation. Eur J Pharmacol. 1982 Jun 4;80(4):377–384. doi: 10.1016/0014-2999(82)90083-8. [DOI] [PubMed] [Google Scholar]
  28. Ward S. J., Takemori A. E. Relative involvement of mu, kappa and delta receptor mechanisms in opiate-mediated antinociception in mice. J Pharmacol Exp Ther. 1983 Mar;224(3):525–530. [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES