Archives of Pharmacal Research

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Attenuation of Morphine Tolerance and Withdrawal Syndrome by Coadministration of Nalbuphine

  • Jang, So-Yong (Department of Neuroscience, College of Medicine, Ewha Womans University) ;
  • Kim, Hee-Jeong (Department of Neuroscience, College of Medicine, Ewha Womans University) ;
  • Kim, Dong-Hyun (Medical Research Institute, College of Medicine, Ewha Womans University) ;
  • Jeong, Myeon-Woo (Department of Pharmacology, National Institute of Toxicological Research, KFDA) ;
  • Ma, Tangen (Department of Pharmacology and Toxicology, University of Mississippi Medical Center) ;
  • Kim, Seong-Youl (Department of Pharmacology and Toxicology, University of Mississippi Medical Center) ;
  • Ho, Ing K. (Department of Pharmacology and Toxicology, University of Mississippi Medical Center) ;
  • Oh, Sei-Kwan (Department of Neuroscience, Medical Research Institute, College of Medicine, Ewha Womans University)
  • Published : 2006.08.01
Download PDF
⟨ Previous Next ⟩

Abstract

Morphine has been used widely on the treatment of many types of chronic pain. However the development of tolerance to and dependence on morphine by repeat application is a major problem in pain therapy. The purpose of the present study was to investigate whether combined administration of nalbuphine with morphine affects the development of tolerance to and dependence on morphine. We hypothesize that the use of nalbuphine, ${\kappa}-agonist$ may prove to be useful adjunct therapy to prevent morphine-induced undesirable effects in the management of some forms of chronic pain. Morphine (10 mg/kg) was injected to rats intraperitoneally for 5 day. The variable dose of nalbuphine (0.1, 1.0 and 5.0 mg/kg) was administered (i.p.) in combination with morphine injection. The development of morphine tolerance was assessed by measuring the antinociceptive effect with the Randall-Selitto apparatus. The development of dependence on morphine was determined by the scoring the precipitated withdrawal signs for 30 min after injection of naloxone (10 mg/kg, i.p.). Nalbuphine did not attenuate antinociceptive effect of morphine in rats. Interestingly, combined administration of morphine with nalbuphine (10:1) significantly attenuated the development of dependence on morphine. The elevation of $[^3H]MK-801$ binding in frontal cortex, dentate gyrus, and cerebellum after chronic morphine infusion was suppressed by the coadministration of nalbuphine. In addition, the elevation of NR1 expression by morphine was decreased by the coadministration of nalbuphine in rat cortex. These results suggest that the coadministration of nalbuphine with morphine in chronic pain treatment can be one of therapies to reduce the development of tolerance to and dependence on morphine.

Keywords

References

  1. Aceto, M. D., Dewey, W. L., Portoghese, P. S., and Takemori, A. E., Effects of beta-funaltrexamine (beta-FNA) on morphine dependence in rats and monkeys. Eur. J. Pharmacol., 123, 387-393 (1986) https://doi.org/10.1016/0014-2999(86)90713-2
  2. Aceto, M. D., Dewey, W. L., Chang, J. K., and Lee, N. M., Dynorphin-(1-13): effects in nontolerant and morphinedependent rhesus monkeys. Eur. J. Pharmacol., 83, 139-142 (1982) https://doi.org/10.1016/0014-2999(82)90279-5
  3. Attali, B., Saya, D., Nah, S. Y., and Vogel, Z., Kappa opiate agonists inhibit $Ca^{2+}$ influx in rat spinal cord-dorsal root ganglion cocultures. Involvement of a GTP-binding protein. J. Biol. Chem., 264, 347-353 (1989)
  4. Bertalmio, A. J. and Woods, J. H., Discriminative stimulus effects of cyclorphane: selective antagonism with naltrexone. Psychopharmacology (Berl), 106, 189-194 (1992) https://doi.org/10.1007/BF02801971
  5. Chen, J. C., Smith, E. R., Cahill, M., Cohen, R., and Fishman, J. R., The opioid receptor binding of pentazocine, morphine, fentanyl, butorphanol and nalbuphine. Life Sci., 52, 389-396 (1992)
  6. Cherubini, E. and North, R. A., Mu and kappa opioids inhibit transmitter release by different mechanisms. Proc. Natl. Acad. Sci. U.S.A., 82, 1860-1863 (1985)
  7. Di Chiara, G. and Imperato, A., Oposite effects of mu and kappa opiate agonists on dopamine release in the nucleus accumbens and in the dorsal caudate of freely moving rats. J. Pharmacol. Exp. Ther., 244, 1076-1080 (1988)
  8. Dickenson, A. H., Neurotransmitters, Drugs and Disease, in Webster R. A. and Jordan C. C. (Ed), Blackwell Scientific Publications, Oxford, p265 (1989)
  9. Franklin, K. B. J. and Paxinos, G., The mouse brain in stereotaxic coordinates, Academic Press, San Diego, CA (1997)
  10. Fukagawa, Y., Katz, J. L., and Suzuki, T., Effects of a selective kappa-opioid agonist, U-50,488H, on morphine dependence in rats. Eur. J. Pharmacol., 170, 47-51 (1989) https://doi.org/10.1016/0014-2999(89)90132-5
  11. Huidobro-Taro, J. P. and Parada, S., Kappa-opiates and urination: pharmacological evidence for an endogenous role of the kappa-opiate receptor in fluid and electrolyte balance. Eur. J. Pharmacol., 107, 1-10 (1984) https://doi.org/10.1016/0014-2999(84)90084-0
  12. Gringauz, M., Rabinowitz, R., Stav, A., and Korczyn, A. D., Tolerance to the analgesic effect of buprenorphine, butorphanol, nalbuphine, and cyclorphan, and cross-tolerance to morphine. J. Anesth., 15, 204-209 (2001) https://doi.org/10.1007/s005400170004
  13. Kayser, V. and Guilbaud, G., The analgesic effects of morphine but not those of the enkephalinase inhibitor thiorphan, are enhanced in arthritic rats. Brain Res., 267, 131-138 (1983) https://doi.org/10.1016/0006-8993(83)91046-6
  14. Kumor, K. M., Haertzen, C. A., Johnson, R. E., Kocher, T., and Jasinsi, D., Human psychopharmacology of ketocyclazocine as compared with cyclazocine, morphine and placebo. J. Pharmacol. Exp. Ther., 238, 960-968 (1986)
  15. Laurie, D. J. and Seeburg, P. H., Ligand affinities at recombination N-methyl-D-aspartate receptors depend on subunit composition. Eur. J. Pharmacol. Mol. Pharmacol. Sect., 268, 335-345 (1994) https://doi.org/10.1016/0922-4106(94)90058-2
  16. Lord, J. A. H., Waterfield, A. A., Hughes, J., and Kostrlitz, H. W., Endogenous opioid peptides: multiple agonists and receptors. Nature, 267, 495-499 (1977) https://doi.org/10.1038/267495a0
  17. Martin, W. R., Eades, C. G., Thompson, J. A., Huppler, R. E., and Gilbert, P. E., The effects of morphine- and nalorphinelike drugs in the nondependent and morphine-dependent chronic spinal dog. J. Pharmacol. Exp. Ther., 197, 517-532 (1976)
  18. Millan, M. J., Kappa-opioid receptors and analgesia. Trends Pharmacol. Sci., 11, 70-76 (1990) https://doi.org/10.1016/0165-6147(90)90321-X
  19. Narita, M. Opioid-regulated pharmacological interaction and intracellular signaling mechanism. Dissertation for Ph.D., Hoshi University, Tokyo, Japan (1992)
  20. Oh, S., Kim, J. I., Chung, M. W., and Ho, I. K., Modulation of NMDA receptor subunit mRNA in butorphanol-tolerant and – withdrawing rats. Neurochem. Res., 25, 1603-1611 (2000) https://doi.org/10.1023/A:1026618603795
  21. Penning, J. P., Samson, B., and Baxter, A. D., Reversal of epidural morphine-induced respiratory depression and pruritus with nalbuphine. Can. J. Anaesth., 35, 599-604 (1988) https://doi.org/10.1007/BF03020347
  22. Pfeiffer, A., Brantl, V., Herz, A., and Emrich, H. M., Psychotomimesis mediated by kappa opiate receptors. Science, 233, 774-776 (1986) https://doi.org/10.1126/science.3016896
  23. Pick, C. G., Paul, D., and Pastemak, G. W., Nalbuphine, a mixed kappa 1 and kappa 3 analgesic in mice. J. Pharmacol. Exp. Ther., 262, 1044-1050 (1992)
  24. Picker, M. J., Yarbrough, J., Hughes, C. E., Smith, M. A., Morgan, D., and Dykstra, L. A., Agonist and antagonist effect of mixed action opioids in the pigeon drug discrimininant procedure: influence of training dose, intrinsic efficacy and interanimal differences. J. Pharmacol. Exp. Ther., 266, 756- 767 (1993)
  25. Pillai, N. P. and Ross, D. H., Interaction of kappa receptor agonists with $Ca^{2+}$ channel antagonists in the modulation of hypothermia. Eur. J. Pharmacol., 132, 237-244 (1986) https://doi.org/10.1016/0014-2999(86)90610-2
  26. Rothman, R. B., Long, J. B., Bykov, V., Jacobson, A. E., Rice, K. C., and Holaday J. W., ${\beta}$-FNA binds irreversibly to the opiate receptor complex: in vivo and in vitro evidence. J. Pharmacol. Exp. Ther., 247, 405-416 (1988)
  27. Rawal, N., Mollefors, K., Axelsson, K., Lingardh, G., and Widman B., An experimental study of urodynamic effects of epidural morphine and of naloxone reversal. Anesth. Analg., 62, 641-647 (1983)
  28. Sakurai, S. Y., Penny, J. B., and Young, A. B., Regionally distinct N-methyl-D-aspartate receptors distinguished by quantitative autoradiography of [$^{3}H$]MK-801 binding in rat brain. J. Neurochem., 60, 1344-1353 (1993) https://doi.org/10.1111/j.1471-4159.1993.tb03295.x
  29. Schmidt, W. K., Tam, S. W., Shotzberger, G. S., Smith, D. H. Jr, Clark, R., and Vernier, V. G., Nalbuphine. Drug Alcohol Depend., 14, 339-362 (1985) https://doi.org/10.1016/0376-8716(85)90066-3
  30. Shippenberg, T. S., Emmett-Oglesby, N. W., Ayesta, F. J., and Herz, A., Tolerance and selective cross-tolerance to the motivational effects of opioids. Psychopharmacology, 96, 110-115 (1988) https://doi.org/10.1007/BF02431542
  31. Sofuoglu, M., Portoghese, P. S., and Takemori, A. E., Maintenance of acute morphine tolerance in mice by selective blockage of kappa opioid receptors with norbinaltorphimine. Eur. J. Pharmacol., 210, 159-162 (1992) https://doi.org/10.1016/0014-2999(92)90666-R
  32. Spanagel, R., Herz, A., and Shippenberg, T. S., Opposing tonically active endogenous opioid systems modulate the mesolimbic dopaminergic pathway. Proc. Natl. Acad. Sci. U.S.A., 89, 2046-2050 (1992)
  33. Suzuki, T., Funada, M., Narit, M., Misawa M., and Nagase H., Pertussis toxin abolishes mu- and delta-opioid agonistinduced place preference. Eur. J. Pharmacol., 205, 85-88 (1991) https://doi.org/10.1016/0014-2999(91)90774-K
  34. Suzuki, T., Fukagawa, Y., Yoshii, T., and Yanaura, S., Effect of opioid agonist-antagonist interaction on morphine dependence in rats. Life Sci., 42, 2729-2737 (1988) https://doi.org/10.1016/0024-3205(88)90250-0
  35. Suzuki, T. and Misawa, M., Physical dependence on morphine using the mu receptor deficient CXBK mouse. Prog. Clin. Biol. Res., 328, 519-522 (1990)
  36. Tokuyama, S., Wakabayashi, H., and Ho, I. K., Direct evidence for a role of glutamate in the expression of the opioid withdrawal syndrome. Eur. J. Pharmacol., 295, 123-129 (1996) https://doi.org/10.1016/0014-2999(95)00645-1
  37. Tokuyama, S., Zhu, H., Oh, S., Ho, I. K., and Yamamoto, T., Further evidence for a role of NMDA receptors in the locus coeruleus in the expression of withdrawal syndrome from opioids. Neurochem. Int., 39, 103-109 (2001) https://doi.org/10.1016/S0197-0186(01)00019-5
  38. Walker, E. A. and Young, A. M., Discriminative-stimulus effects of the low efficacy ${\mu}$agonist nalbuphine. J. Pharmacol Exp. Ther., 267, 322-330 (1993)
  39. Werz, M. A. and MacDonald, R. L., Dynorphin and neoendorphin peptides decrease dorsal root ganglion neuron calciumdependent action potential duration. J. Pharmacol. Exp. Ther., 234, 49-56 (1985)
  40. Zhu, H. and Ho, I. K., NMDA-R1 antisense attenuates morphine withdrawal behaviors. Eur. J. Pharmacol., 352, 151-156 (1998) https://doi.org/10.1016/S0014-2999(98)00367-7