YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

The Development of Tolerance to and Dependence on Morphine are Reduced by Co-administration of Nalbuphine in Rat

Nalbuphine의 병용투여에 의한 morphine의 내성 및 의존성 형성 저하효과

  • 정면우 (국립독성연구원 약리부) ;
  • 임화경 (국립독성연구원 약리부) ;
  • 전용준 (국립독성연구원 약리부) ;
  • 김혜정 (국립독성연구원 약리부) ;
  • 박인숙 (국립독성연구원 약리부) ;
  • 오우용 (국립독성연구원 약리부) ;
  • 왕소영 (국립독성연구원 약리부) ;
  • 박윤주 (국립독성연구원 약리부) ;
  • 강주희 (국립독성연구원 약리부)
  • Published : 2002.08.01
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 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, k-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 days. 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 tolerance to morphine 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 20 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 (100:1) significantly attenuated the development of morphine tolerance and dependence. These results suggest that the co-administration of nalbuphine with morphine in chronic morphine treatment can be one of therapies to reduce the development of dependence on morphine.

Keywords

References

  1. Yaksh, T. L. : Tolerance: Factors involved in changes in the dose-effect relationship with chronic drug exposure. In: Towards a New Pharmacotherapy of Pain (Basbaum, A. I., Bessan, J.-M., Eds.), Wiley, Chichester, UK, p. 157 (1991)
  2. Houde, R. W., Wallenstein, S. L. and Beaver, W. T. : Evaluation of analgesics in patients with cancer pain. In: International Encyclopedia of Pharmacology and Therapeutics (Lasagna, L., Ed.), Section 6, 1. Clinical Pharmacology. Pergamon, Oxford. p. 59 (1996)
  3. Foley, K. M. : Clinical tolerance to opioids. In: Towards a New Pharmacotherapy of Pain (Basbaum, A. I.,Bessan, J.-M., Eds.), Wiley, Chichester; UK. p. 181 (1991)
  4. Portenoy, R. K. : Tolerance to opioid analgesics: Clinical aspects. In: Cancer Surveys, Vol. 21, Palliative Medicine: Problem Areas in Pain and Symptom Management. Imperial Cancer Research Fund. p. 49 (1994)
  5. Ling, G. S. F., Simantov, R. and Pasternak, G. W. : Differential development of acute tolerance to analgesia, respiratory depression, gastrointestinal transit and hormone release in a morphine infusion model. Life Sci. 45, 1627 (1989) https://doi.org/10.1016/0024-3205(89)90272-5
  6. McGilliar, K. L. and Takemori, A. E. : Alterations in the antagonism by naloxone of morphine-induced respiratory depression and analgesia after morphine pretreatment. J. Pharmacol. Exp. Ther. 207, 884 (1978)
  7. Suzuki, T., Narita, M., Takahashi, Y, Misawa, M. and Nagase, H. : Effects of nor-binaltorphimine on the development of analgesic tolerance to and physical dependence on morphine. Eur. J. Pharmacol. 213, 91 (1992) https://doi.org/10.1016/0014-2999(92)90237-X
  8. Schmidt, W. K., Tam, S. W. and Shotzberger; G. S. : Nalbuphine. Drug Alcohol Depend. 14, 339 (1985) https://doi.org/10.1016/0376-8716(85)90066-3
  9. Pick, C. G., Paul, D. and Pasternak, G. W. : Nalbuphine, a mixed $\kappa$1 and $\kappa$3 analgesic in mice. J. Pharmacol. Exp. Ther. 262, 1044 (1992)
  10. De Souza, E. B., Schmidt, W. K. and Kuhar, M. J. : Nalbuphine: an autoradiographic opioid receptor binding profile in the central nervous system of an agonist/antagonist analgesic. J. Pharmacol. Exp. Ther. 244, 391 (1988)
  11. Walker, E. A. and Young, A. M. : Discriminative-stimulus effects of the low efficacy $\mu$ agonist nalbuphine.J. Pharmacol. Exp. Ther. 267, 322 (1993)
  12. Chen, J. C., Smith, E. R. and Cahill, M. : The opioid receptor binding of dezocine, morphine, fentanyl, butorphanol and nalbuphine. Life Sci. 52, 389 (1992)
  13. Bailey, P. L., Clark, N. J. and Pace, N. L. : Antagonism of postoperative opioid-induced respiratory depression: nalbuphine versus naloxone. Anesth. Analg. 66, 1109 (1987)
  14. Davies, G. G. and From, R. A. : Blinded study using nalbuphine for prevention of pruritus induced by epidural fentanyl. Anesthesiology. 69, 763 (1988) https://doi.org/10.1097/00000542-198809010-00763
  15. Baxter, A. D., Samson, B. and Penning, J. P. : Prevention of epidural morphine-induced respiratory depression with intravenous nalbuphine infusion in post-thoractomy patients. Can. J. Anaesth., 36, 503 (1989)
  16. Cohen, S. E., Ratner, E. F. and Kreitzman, T. R. : Nalbuphine is better than naloxone for treatment of side effects after epidural morphine. Anaesth. Analg. 75, 747 (1992)
  17. Mills, C. A., Flacke, J. W. and Flacke, W. E. : Narcotic reversal in hypercapnic dogs: comparison of naloxone and nalbuphine. Can. J. Anaesth. 37, 238 (1990)
  18. Mushlin, B. E. and Cochin, J, : Tolerance to morphine in the rat: its prevention by naloxone. Life Sci. 18, 797 (1976)
  19. Yano, I. and Takemori, A. E. : Inhibition by naloxone of tolerance and dependence in mice treated acutely and chronically with morphine. Res. Commun. Chem. Pathol. Pharmacol. 16, 721 (1977)
  20. Kayer, 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 (1983) https://doi.org/10.1016/0006-8993(83)91046-6
  21. Rattan, A. K. and Sribanditmongkol, P. : Effect on morphineinduced catalepsy, lethality, and analgesia by a benzodiazepine receptor agonist midazolam in the rat. Pharmacol. Biochem. Behav. 48, 357 (1994) https://doi.org/10.1016/0091-3057(94)90538-X
  22. Carlezon, W. A., Kosten, T. A. and Nestler, E. J, : Behavioral interactions caused by combined administration of morphine and MK-801 in rats. Psychopharmacology. 151, 261 (2000) https://doi.org/10.1007/s002130000462
  23. Yamamoto, T., Ohno, M. and Ueki, S.: A selective $\kappa$ -opioid agonist, U-50, 488H, blocks the development of tolerance to morphine analgesia in rats. Eur. J. Pharmacol. 156, 173 (1988) https://doi.org/10.1016/0014-2999(88)90162-8
  24. Tao, P. L., Hwang, C. L. and Chen, C. Y. : U-50,488 blocks the development of morphine tolerance and dependence at a very low dose in guinea pigs. Eur. J. Pharmacol. 256, 281 (1994) https://doi.org/10.1016/0014-2999(94)90553-3
  25. Takemori, A. E., Loh, H. H. and Lee, N. M. : Suppression by dynorphin A-(1-13) of the expression of opiate withdrawal and tolerance in mice. Eur. J. Pharmacol. 221, 223 (1992) https://doi.org/10.1016/0014-2999(92)90705-9
  26. Green, P. G. and Lee, N. M. : Dynorphin A-(1-13) attenuates withdrawal in morphine-dependent rats: effect of route of administration. Eur. J. Pharmacol. 145, 267 (1988)
  27. DeLander, G. E., Portoghese, P. S. and Takemori, A. E. : Role of spinal $\mu$ opioid receptors in the development of morphine tolerance and dependence. J. Pharmacol. Exp. Ther. 231, 91 (1984)
  28. Yu. V. C. and Sadee, W. : Efficacy and tolerance of narcotic analgesic at the $\mu$ opioid receptor in differential human neuroblastoma cells. J. Pharmacol. Exp. Ther. 245, 350 (1988)
  29. Adams, R. E. and Wooten, G. F. : Is morphine dependence mediated exclusively by the $\mu$ receptor? Neurochem. Res. 18, 1041 (1993)
  30. Pande, A. C., Pyke, R. E., Greiner, M., Cooper, S.A., Benjamin, R. and Pierce, M. W. : Analgesic efficacy of the kappa-receptor agonist, enadoline, in dental surgery pain. Clin. Neuropharmacol: 19, 92 (1996)
  31. Von Voigtlander, P. F. and Lewis, R A. : U-50,488, a selective kappa opioid agonist: comparison to other reputed kappa agonists. Prog. Neuropsychopharmacol Biol. Psychiatry. 6, 467 (1982)
  32. Millan, M. J., Czlonkowski, A., Lipkowski, A. and Herz, A.: Kappa-opioid receptor-mediated antinociception in the rat. II. Supraspinal in addition to spinal sites of action. J. Pharmacol. Exp. Ther. 251, 342 (1989)
  33. Takemori, A. E., Ho, B. Y., Naeseth, J. S. and Portoghese, P. S. : Nor-binaltorphimine, a highly selective kappa-opioid antagonist in analgesic and receptor binding assays. J. Pharmacol. Exp. Ther. 246, 255 (1988)
  34. Herman, B. H. and Goldstein, A. : Antinociception and paralysis induced by intrathecal dynorphin A. J. PharmacoL Exp. Ther. 232, 27 (1985)
  35. Gogas, K. R., Levine, J. D. and Basbaum, A. I. : Differential contribution of descending controls to the antinociceptive actions of kappa and mu opioids: an analysis of formalinevoked C-fos expression. J. Pharmacol. Exp. Ther. 276, 80 (1996)
  36. Stevens, C. W. and Yaksh, T. L. : Dynorphin A and related peptides administered intrathecally in the rat: a search for putative kappa opiate receptor activity.J. Pharmacol. Exp. Ther. 238, 833 (1986)
  37. Leighton, G. E., Rodriguez, R. E., Hill, R. G. and Hughes, J. : kappa-Opioid agonists produce antinociception after i.v. and i.c.v. but not intrathecal administration in the rat. Br. J. Pharmacol. 93, 553 (1988)
  38. Tiseo, P. J., Geller, E. B. and Adler, M. W. : Antinociceptive action of intracerebroventricularly administered dynorphin and other opioid peptides in the rat. J. Pharmacol. Exp. Ther. 246, 449 (1988)
  39. Tulunay, F. C., Jen, M. F., Chang, J. K., Loh, H. H. and Lee, N. M. : Possible regulatory role of dynorphin on morphine- and beta-endorphin-induced analgesia. J. Pharmacol. Exp. Ther. 219, 296 (1983)
  40. Friedman, H. J., Jen, M. F., Chang, J, K., Lee, N. M. and Loh, H. H. : Dynorphin: a possible modulatory peptide on morphine or beta-endorphin analgesia in mouse. Eur. J. Pharmacol. 69, 357 (1981)
  41. Ramarao, P., Jablonski, J, H. I., Rehder, K. R. and Bhargava, H. N. : Effect of kappa-opioid receptor agonists on morphine analgesia in morphine-naive and morphine-tolerant rats. Eur. J. Pharmacol. 156, 239 (1988) https://doi.org/10.1016/0014-2999(88)90327-5
  42. Bhargava, H. N. : Diversity of agents that modify opioid tolerance, physical dependence, abstinence syndrome, and self-administrative behavior. Pharmacol. Rev. 46, 293 (1994)
  43. Rothman, R. B. : A review of the role of anti-opioidpeptides in morphine tolerance and dependence. Synapse. 12, 129 (1992) https://doi.org/10.1002/syn.890120206
  44. Schmauss,C. and Herz, A. : Intrathecally administered dynorphin(1-17) modulates morphine-induced antinociception differently in morphine-naive and morphine-tolerant rats. Eur. J. Pharmacol. 135, 429 (1987) https://doi.org/10.1016/0014-2999(87)90695-9
  45. Hooke, L. P., He, L. and Lee, N. M. : Dynorphin A modulates acute and chronic opioid effects. J. Pharmacol. Exp. Then 273, 292 (1995)
  46. Takahashi, M., Senda, T. and Kaneto, H. : Role of spinal kappa opioid receptors in the blockade of the development of antinociceptive tolerance to morphine. Eur. J. Pharmacol. 200, 293 (1991) https://doi.org/10.1016/0014-2999(91)90585-E
  47. Cowan, A., Zhu, X. Z., Mosberg, H. I., Omnaas, J. R. and Porreca, E : Direct dependence studies in rats with agents selective for different types of opioid receptor. J. Pharmacol. Exp. Ther. 246, 950 (1988)
  48. Suzuki, T., Hayashi, Y. and Misawa, M. : The role of mu1 receptor in physical dependence on morphine using the mu receptor deficient CXBK mouse. Life Sci. 50, 849 (1992) https://doi.org/10.1016/0024-3205(92)90203-2
  49. Fukagawa, Y., Katz, J.L. and Suzuki, T. : Effects of a selective kappa-opioid, U50488H, on morphine dependence in rats. Eur. J. Pharmacol. 170, 47 (1989) https://doi.org/10.1016/0014-2999(89)90132-5
  50. Penning, J., Samson, B. and Baxter, A.D. : Reversal of epidural morphine-induced respiratory depression and pruritus with nalbuphine. Can. J. Anaesth. 35, 599 (1988) https://doi.org/10.1007/BF03020347