Morphine metabolites

Acta Anaesthesiologica Scandinavica

Volumn 41, Issue 1 II, 1997, Pages 116-122

  Christrup, L L ^a  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

morphine; morphine metabolites; morphine 3 glucuronide (M3G); morphine 6 glucuronide (M6G)

Indexed keywords

DRUG METABOLITE; MORPHINE; MORPHINE 3 GLUCURONIDE; MORPHINE 6 GLUCURONIDE; MORPHINE DERIVATIVE;

ANALGESIC ACTIVITY; ANTINOCICEPTION; CONFERENCE PAPER; DRUG EFFECT; DRUG METABOLISM; DRUG POTENCY; DRUG STRUCTURE; DRUG TOLERANCE; HUMAN; PAIN; PRIORITY JOURNAL;

EID: 0031032492     PISSN: 00015172     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1399-6576.1997.tb04625.x     Document Type: Conference Paper

References (80)

1. Sertürner FW. Darstellung der reinen Mohnsäure (Opiumsäure) nebst einer chemischen Untersuchung des Opiums mit vorzüglicher Hinsicht auf einen darin neuen Stoff und die dahin gehöringen Bemerkungen. Trommdorfs J Pharm 1806: 14: 47-93.
2. Gulland JM, Robinson R. The morphine group. Part I. A discussion of the constitutional problem. J Chem Soc 1923: 1923: 980-998.
3. Van Duin CF, Robinson R, Smith JC. The morphine group. Part III. The constitution of neopine. J Chem Soc 1923: 1926: 903-908.
4. Schöpf C. Die konstitution der morphiumalkaloide. Ann Chem 1927: 452: 211-267.
5. Gates M, Tschudi G. The synthesis of morphine. J Am Chem Soc 1952: 74: 1109-1110.
6. Gates M, Tschudi G. The synthesis of morphine. J Am Chem Soc 1956: 78: 1380-1393.
7. Adams ML, Morris DL, Brase DA, Dewey WL. Stereoselective effect of morphine on antinociception and endogenous opioid peptide levels in plasma but not cerebrospinal fluid of dogs. Life Sci 1991: 48: 917-924.
8. Budavari S, O'Neil MJ, Smith A, Heckelman PE, Eds. The Merck Index, 11th ed. Rahway: N.J. Merck and Co. Inc., 1989: 988.
9. Vree TB, Verwey-Van Wissen CPWGM. Pharmacokinetics and metabolism of codeine in humans. Biopharm Drug Dispos 1992: 13: 445-460.
10. Säwe J, Dahlström B, Paalzow L, Rane A. Morphine kinetics in cancer patients. Clin Pharmacol Ther 1981: 30:629-635.
11. Säwe J, Kager L, Svensson JO, Rane A. Morphine metabolism in cancer patients on increasing oral doses - no evidence for autoinduction or dose dependence. Br J Clin Pharmacol 1985: 19: 495-501.
12. Osborne R, Joel S, Trew D, Slevin M. Morphine and metabolite behaviour after different routes of morphine administration: demonstration of the importance of the active metabolite morphine-6-glucuronide. Clin Pharmacol Ther 1990: 47: 12-19.
13. Brunk FS, Delle M. Morphine metabolism in man. Clin Pharmacol Ther 1974: 16: 51-57.
14. Yeh SY. Urinary excretion of morphine and its metabolites in morphine-dependent subjects. J Pharmacol Exp Ther 1975: 192: 201-210.
15. Boerner U, Abbott S, Roe RL. The metabolism of morphine and heroin in man. Drug Matab Rev 1975: 112: 39-73.
16. Bodenham A, Quinn K, Park GR. Extrahepatic morphine metabolism in man during the anhepatic phase of orthotopic liver transplantation. Br J Anaesth 1989: 63:380-384.
17. Yue Q, Odar-Cederlöf I, Svensson JO, Säwe J. Glucuronidation of morphine in human kidney microsomes. Pharmacol Toxicol 1988: 63: 337-341.
18. Wahlström A, Winblad B, Bixo M, Rane A. Human brain metabolism of morphine and naloxone. Pain 1988: 35: 121-127.
19. Oguri K, Ida S, Youshimura H, Tsukamoto H. Metabolism of drugs: LXIX studies on the urinary metabolites of morphine in several mammalian species. Chem Pharm Bull 1970: 18: 2414-2419.
20. Yeh SY, Gorodetzky CW, Krebs HA. Isolation and identification of morphine 3- and 6-glucuronides, morphine 3,6-diglucuronide, morphine 3-ethereal sulfate, nor-morphine, and normorphine 6-glucuronide as morphine metabolites in humans. J Pharm Sci 1977: 66: 1288-1293.
21. Hoskin PJ, Hanks GW. Morphine: pharmacokinetics and clinical practice. Br J Cancer 1990: 62: 705-707.
22. Chen ZR, Irvine RJ, Somogyi AA, Bochner F. Mu receptor binding of some commonly used opioids and their metabolites. Life Sci 1991: 48: 2165-2171.
23. Sullivan AF, McQuay HJ, Bailey D, Dickenson AH. The spinal antinociceptive actions of morphine metabolites morphine-6-glucuronide and normorphine in the rat. Brain Res 1989: 482: 219-224.
24. Shimomura K, Kamata O, Ueki S, Ida S, Oguri K, Yoshimura H, Tsukamoto H. Analgesic effect of morphine glucuronides. Tohoku J Exp Med 1971: 105: 45-52.
25. Svensson JO, Rane A, Säwe J, Sjöqvist F. Determination of morphine, morphine-3-glucuronide and (tentatively) morphine-6-glucuronide in plasma and urine using ion-pair high-performance liquid chromatography. J Chromatogr 1982: 230: 427-432.
26. Woolner DF, Winter D, Frendin TJ, Begg EJ, Lynn KL, Wright GJ. Renal failure does not impair the metabolism of morphine. Br J Clin Pharmacol 1986: 2: 55-59.
27. Säwe J, Odar-Cederlöf I. Kinetics of morphine in patients with renal failure. Eur J Clin Pharmacol 1987: 32: 377-382.
28. Milne RW, Nation RL, Somogyi AA, Bochner F, Griggs WM. The influence of renal function on the renal clearance of morphine and its glucuronide metabolites in intensive-care patients. Br J Clin Pharmacol 1992: 34:53-59.
29. Osborne R, Thompson P, Joel S, Trew D, Patel N, Slevin M. The analgesic activity of morphine-6-glucuronide. Br J Clin Pharmacol 1992: 34: 130-138.
30. Glavina JM, Robertshaw R. Myoclonic spasms following intrathecal morphine. Anaesthesia 1988: 43: 389-390.
31. Potter JM, Reid DB, Shaw RJ, Hackett P, Hickmann PE. Myoclonus associated with treatment with high doses of morphine: the role of supplemental drugs. Br Med J 1989: 299: 150-153.
32. Parkinson SK, Bailey SL, Little WL, Mueller JB. Myoclonic seizure activity with chronic high-dose spinal opioid administration. Anesthesiology 1990: 72: 743-745.
33. Sjøgren P, Jonsson T, Jensen N-H, Drenck N-E, Jensen TS. Hyperalgesia and myoclonus in terminal cancer patients treated with continuous intravenous morphine. Pain 1993: 55: 93-97.
34. Sjøgren P Dragsted L, Christensen CB. Myoclonic spasms during treatment with high doses of intravenous morphine in renal failure. Acta Anaesthesiol Scand 1993: 37: 780-782.
35. Morley JS, Miles JB, Wells CJ, Bowsher D. Paradoxical pain. Lancet 1992: 340: 1045.
36. Paul D, Standifer KM, Inturrisi CE, Pasternak GW. Pharmacological characterization of morphine-6β-glucuronide, a very potent morphine metabolite. J Pharmacol Exp Ther 1989: 251: 477-483.
37. 1- and δ-opioid receptors in modulation of fetal EEG and respiratory activity. Am J Physiol 1993: 265: 433-438.
38. 1 receptor-mediated effect. J Pharmacol Exp Ther 1990: 252: 235-240.
39. 5]-enkephalin and partial antagonism ny naltrindole. J Pharmacol Exp Ther 1992: 262: 1004-1010.
40. 2]-deltorphin I. Eur J Pharmacol 1993: 230: 85-88.
41. Pasternak GW, Bodnar RJ, Clark JA, Inturrisi CE. Morphine-6-glucuronide, a potent mu agonist. Life Sci 1987: 41: 2845-2849.
42. Christensen CB, Jorgensen LN. Morphine-6-glucuronide has high affinity for the opioid receptor. Pharmacol Toxicol 1987: 60: 75-76.
43. Oguri K, Yamada-Mori I, Shigezane J, Hirano T, Yoshimura H. Enhanced binding of morphine and nalorphine to opioid delta receptor by glucuronate and sulfate conjugation at the 6-position. Life Sci 1987: 41: 1457-1464.
44. Thompson PI, Hucks D, McLoughlin L, Grossman A, Rees L, Slevin M. Comparative opiate receptor affinities af morphine and its active metabolite morphine-6-glucuronide. Br J Cancer 1990: 62: 484.
45. McLoughlin L, Thompson PI, Hucks D, Grossman A, Rees L. Comparative opiate receptor subsite affinities af morphine and morphine-6-glucuronide. Pain 1990: (suppl.) 52: S187.
46. Francés B, Gout R, Campistron G, Panconi E, Cros J. Morphine-6-glucuronide is more mu-selective and potent in analgesic tests than morphine. Prog Clin Biol Res 1990: 328: 477-480.
47. Christensen CB, Reiff L. Morphine-6-glucuronide: receptor binding profile in bovine caudate nucleus. Pharmacol Toxicol 1991: 68: 151-153.
48. Francés B, Gout R, Monsarrat B, Cros J, Zajac J-M. Further evidence that morphine-6β-glucuronide is a more potent opioid agonist than morphine. J Pharmacol Exp Ther 1992: 262: 25-31.
49. Hucks D, Thompson PI, McLoughlin L, Joel SP, Patel N, Grossman A, Rees LH, Slevin ML. Explanation at the opioid receptor level for differing toxicity of morphine and morphine-6-glucuronide. Br J Cancer 1992: 65: 122-126.
50. Mignat C, Wille U. Affinity for morphine receptor subtypes is differently influenced by substitution of morphine at C3 and C6. Arch Pharmacol 1994: (suppl.) 349: 348.
51. Mignat C, Wille U, Ziegler A. Affinity profiles of morphine, codeine, dihydrocodeine and their glucuronides at opioid receptor subtypes. Life Sci 1995: 56: 793-799.
52. Goucke RC, Hackett LP, Ilett KF. Concentrations of morphine, morphine-6-glucuronide and morphine-3-glucuronide in serum and cerebrospinal fluid following morphine administration to patients with morphine-resistant pain. Pain 1994: 56: 145-149.
53. Gaillard P, Carrupt P-A, Testa B. The conformation-dependent lipophilicity of morphine glucuronides as calculated from their molecular lipophilicity potential. Bioorg Med Chem Lett 1994: 4: 737-742.
54. Carrupt P-A, Testa B, Bechalany A, El Tayar N, Descas P, Perrissoud D. Morphine 6-glucuronide and morphine 3-glucuronide as molecular chameleons with unexpected lipophilicity. J Med Chem 1991: 34: 1272-1276.
55. Suzuki N, Kalso E, Rosenberg PH. Intrathecal morphine-3-glucuronide does not antagonize spinal antinociception by morphine or morphine-6-glucuronide in rats. Eur J Pharmacol 1993: 249: 247-250.
56. Gong Q-L, Hedner J, Björkman R, Hedner T. Morphine-3-glucuronide may functionally antagonize morphine-6-glucuronide induced antinociception and ventilatory depression in the rat. Pain 1992: 48: 249-255.
57. Gong Q-L, Hedner T, Hedner J, Björkman R, Nordberg G. Antinociceptive and ventilatory effects of the morphine metabolites: morphine-6-glucuronide and morphine-3-glucuronide. Eur J Pharmacol 1991: 193: 47-56.
58. Abbott FV, Palmour RM. Morphine-6-glucuronide: analgesic effects and receptor binding profile in rats. Life Sci 1988: 43: 1685-1695.
59. Osborne R, Joel S, Trew D, Slevin M. Analgesic activity of morphine-6-glucuronide. Lancet 1988: I: 828.
60. Osborne RJ. Clinical pharmacology of morphine and morphine glucuronides: the role of the active metabolite morphine-6-glucuronide. London: London University 1988. MD Thesis.
61. Thompson PI, John L, Wedzicha JA, Slevin ML. Comparison of the respiratory depression induced by morphine and its active metabolite morphine-6-glucuronide. Br J Cancer 1990: 62: 484.
62. Hanna MH, Peat SJ, Woodham M, Knibb A, Fung C. Analgesic efficacy and CSF pharmacokinetics of intrathecal morphine-6-glucuronide: comparison with morphine. Br J Anaesth 1990: 64: 547-550.
63. Pellegrino DA, Riegler FX, Albrecht RF. Ventilatory effect of fourth cerebroventricular infusion of morphine-6 or morphine-3-glucuronide in the awake dog. Anesthesiology 1989: 71: 936-940.
64. Hanna MH, Peat SJ, Knibb AA, Fung C. Disposition of morphine-6-glucuronide and morphine in healthy volunteers. Br J Anaesth 1991: 66: 103-107.
65. Peat SJ, Hanna MH, Woodham M, Knibb AA, Ponte J. Morphine-6-induced effect on ventilation in normal volunteers. Pain 1991: 45: 101-104.
66. Massi P, Giagnoni G, Basilico L, Gori E, Rubino T, Parolaro D. Intestinal effect of morphine-6-glucuronide in vivo and in vitro characterization. Eur J Pharmacol 1994: 253: 269-274.
67. Schmidt N, Brune K, Geisslinger G. Opioid receptor agonist properties of morphine and morphine-6-glucuronide in the guinea-pig ileum. Eur J Pharmacol 1994: 255: 245-247.
68. Igawa Y, Westerling D, Mattiasson A, Andersson K-E. Effects of morphine metabolites on micturition in normal, unanaesthesized rats. Br J Pharmacol 1993: 110: 257-262.
69. Chapman DJ. Analysis and pharmacokinetics of morphine and morphine-6-glucuronide. Guildford: University of Surrey, 1990. Ph.D Thesis.
70. Hanna MH, D'Costa F, Peat SJ, Fung C, Venkat N, Zilkha TR. Morphine-6-glucuronide disposition in renal impairment. Br J Anaesth 1993: 70: 511-514.
71. Smith MT, Watt JA, Cramond T. Morphine-3-glucuronide - a potent antagonist of morphine analgesia. Life Sci 1990: 47: 579-585.
72. Ekblom M, Gårdmark M, Hammerlund-Udenaes M. Pharmacokinetics and pharmacodynamics of morphine-3-glucuronide in rats and its influence on the antinociceptive effect of morphine. Biopharm Drug Dispos 1993: 14: 1-11.
73. Hewett K, Dickenson AH, McQuay HJ. Lack of effect of morphine-3-glucuronide on the spinal antinociceptive actions of morphine in the rat: an electrophysiological study. Pain 1993: 53: 59-63.
74. Lipkowsky AW, Carr DB, Langlade A, Osgod PF, Szyfelbein SK. Morphine-3-glucuronide: silent regulator of morphine actions. Life Sci 1994: 55: 149-154.
75. Yaksh TL, Harty GJ, Onofrio BM. High doses of spinal morphine produce a nonopiate receptor mediated hyperesthesia: clinical and theoretic implications. Anesthesiology 1986: 64: 590-597.
76. Woolf CJ. Intrathecal high dose morphine produces hyperalgesia in the rat. Brain Res 1981: 209: 491-495.
77. Yaksh TL, Harty GJ. Pharmacology of the allodynia in rats evoked by high dose intrathecal morphine. J Pharmacol Exp Ther 1987: 244: 501-507.
78. Labella FS, Pinsky C, Havlicek V. Morphine derivatives with diminished opiate receptor potency show enhanced central excitatory activity. Brain Res 1979: 174: 263-271.
79. A receptor complex. Life Sci 1994: 54: 687-694.
80. Bartlett SE, Dodd PR, Smith MT. Pharmacology of morphine and morphine-3-glucuronide at opioid, excitatory amino acid, GABA and glycine binding sites. Pharmacol Toxicol 1994: 75: 73-81.