Techniques in Regional Anesthesia & Pain Management
Volume 11, Issue 1 , Pages 27-32 , January 2007

Peripherally restricted μ-opioid receptor antagonists: a review

  • Andrew J. Linn, MD

      Affiliations

    • Corresponding Author InformationAddress reprint requests and correspondence: Richard A. Steinbrook, MD, Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, FD 407, Boston, MA 02215.
    • ,
  • Richard A. Steinbrook, MD

References 

  1. Wood JD, Galigan JJ. Function of opioids in the enteric nervous system. Neurogastroenterol Motil. 2004;16:17–28
  2. Holzer P. Opioids and opioid receptors in the enteric nervous system: from a problem in opioid analgesia to a possible new prokinetic therapy in humans. Neurosci Lett. 2004;361:192–195
  3. Levy MH. Pharmacological treatment of cancer pain. N Engl J Med. 1996;335:1124–1136
  4. Laxatives for the management of constipation in palliative care patients. Cochrane Database Syst Rev. 2006;4:CD003448
  5. Bell T, Leslie J, Annunziata K, et al. Opioid-induced constipation compromises pain management and impacts patient quality of life. AAPM. 2007;161
  6. Abbound TK, Lee K, Zhu J, et al. Prophylactic oral naltrexone with intrathecal morphine for cesarean section: effects on adverse reactions and analgesia. Anesth Analg. 1990;71:367–370
  7. Syke N. Oral naloxone in opioid-associated constipation. Lancet. 1991;337:1475
  8. Culpepper-Morgan JA, Inturrisi CE, Portenoy RK, et al. Treatment of opioid-induced constipation with oral naloxone: a pilot study. Clin Pharmacol Ther. 1992;52:90–95
  9. Latasch L, Zimmermann M, Eberhardt B, et al. Treatment of morphine-induced constipation with oral naloxone. Anaesthesist. 1997;46:191–194
  10. Meissner W, Schmidt U, Hartmann M, et al. Oral naloxone reverses opioid-associated constipation. Pain. 2000;84:105–109
  11. Yuan CS, Foss JF, Osinski J, et al. The safety and efficacy of oral methylnaltrexone in preventing morphine-induced delay in oral-cecal transit time. Clin Pharmacol Ther. 1997;61:467–475
  12. Yuan CS, Foss JF, O’Connor M, et al. Effects of enteric-coated methylnaltrexone in preventing opioid-induced delay in oral-cecal transit time. Clin Pharmacol Ther. 2000;67:398–404
  13. Liu SS, Hodgson PS, Carpenter RL, et al. ADL 8-2698, a trans-3,4-dimethyl-4-(3-hydroxyphenyl) piperidine, prevents gastrointestinal effects of intravenous morphine without affecting analgesia. Clin Pharmacol Ther. 2001;69:66–71
  14. Yuan CS, Foss JF, O’Connor M, et al. Methylnaltrexone for reversal of constipation due to chronic methadone use: a randomized controlled trial. J Am Med Assoc. 2000;283:367–372
  15. Yuan CS, Wei G, Foss JF, et al. Effects of subcutaneous methylnaltrexone on morphine-induced peripherally mediated side effects: a double-blind randomized placebo-controlled trial. J Pharmacol Exp Ther. 2002;300:118–123
  16. Paulson DM, Kennedy DT, Donovick RA, et al. Alvimopan: an oral, peripherally acting, mu-opioid receptor antagonist for the treatment of opioid-induced bowel dysfunction: a 21-day treatment-randomized clinical trial. J Pain. 2005;3:184–192
  17. Gonenne J, Camilleri M, Ferber I, et al. Effect of alvimopan and codeine on gastrointestinal transit: a randomized controlled study. Clin Gastroenterol Hepatol. 2005;8:784–791
  18. Luckey A, Livingston E, Tache Y. Mechanisms and treatment of postoperative ileus. Arch Surg. 2003;138:206–214
  19. Delaney CP, Senagore AJ, Viscusi ER, et al. Postoperative upper and lower gastrointestinal recovery and gastrointestinal morbidity in patients undergoing bowel resection: pooled analysis of placebo data from 3 randomized controlled trials. Am J Surg. 2006;91:315–319
  20. Livingston EH: personal communication, Sept 29, 2006
  21. Kalff JC, Turler A, Schwarz NT, et al. Intra-abdominal activation of a local inflammatory response within the human muscularis externa during laparotomy. Ann Surg. 2003;237:301–315
  22. Bult H, Boeckxstaens GE, Pelcksman PA, et al. Nitric oxide as an inhibitory non-adrenergic non-cholinergic neurotransmitter. Nature. 1990;345:346–347
  23. DeJonge W, VanDenWijngaard R, The F, et al. Postoperative ileus is maintained by intestinal immune infiltrates that activate inhibitory neural pathways in mice. Gastroenterology. 2003;125:1137–1147
  24. Cali RL, Meade PG, Swanson MS, et al. Effect of morphine and incision length on bowel function after colectomy. Dis Colon Rectum. 2000;43:163–168
  25. Shahbazian A, Heineman A, Schmidhammer H, et al. Involvement of mu- and kappa-, but not delta-, opioid receptors in the peristaltic motor depression caused by endogenous and exogenous opioids in the guinea-pig intestine. Br J Pharmacol. 2002;135:741–750
  26. Wolff BG, Michelassi F, Gerkin TM, et al. Alvimopan, a novel, peripherally acting mu opioid antagonist: results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial of major abdominal surgery and postoperative ileus. Ann Surg. 2004;240:728–735
  27. Delaney CP, Weese J, Hyman N, et al. Phase III trial of alvimopan, a novel, peripherally acting, mu opioid antagonist, for postoperative ileus after major abdominal surgery. Dis Colon rectum. 2005;48:1114–1129
  28. Viscusi ER, Goldstein S, Witkowski T, et al. Alvimopan, a peripherally acting mu-opioid receptor antagonist, compared with placebo in postoperative ileus after major abdominal surgery. Surg Endosc. 2006;20:64–70
  29. Leslie J, Steinbrook R, Viscusi E, et al. Alvimopan oral dosing 30-90 minutes before and BID after bowel resection accelerated GI recovery. Anesthesiology. 2006;105:A122
  30. Gan TJ, Isreal R, Penenberg DN. Methylnaltrexone in post-operative bowel dysfunction: results of a double-blind, randomized, placebo-controlled trial in segmental colectomy patients. IARS Abstract. 2006;S-281
  31. Yuan CS, Foss JF, O’Connor M, et al. Efficacy of orally administered methylnaltrexone in decreasing subjective effects after intravenous morphine. Drug Alcohol Depend. 1998;52:161–165
  32. Foss JF, Bass AS, Goldberg LI. Dose-related antagonism of the emetic effect of morphine by methylnaltrexone in dogs. J Clin Pharmacol. 1993;33:747–751
  33. Foss JF, Yuan CS, Roizen MF, et al. Prevention of apomorphine-induced. or cisplatin-induced emesis in the dog by a combination of methylnaltrexone and morphine. Cancer Chemother Pharmacol. 1998;33:747–751
  34. Moerman I, Franck P, Camu F. Evaluation of methylnaltrexone for the reduction of postoperative vomiting and nausea incidencies. Act Anaesthesiol Belg. 1995;46:127–132
  35. Vallejo R, de Leon-Casasola O, Benyamin R. Opioid therapy and immunosuppression: a review. Am J Ther. 2004;11:354–365
  36. Ho WZ, Guo CJ, Yuan CS, et al. Methylnaltrexone antagonizes opioid-mediated enhancement of HIV infection of human blood mononuclear phagocytes. J Pharmacol Exp Ther. 2003;307:1158–1162
  37. Gupta K, Kshirsagar S, Chang L, et al. Morphine stimulates angiogenesis by activating proangiogenic and survival-promoting signaling and promotes breast tumor growth. Cancer Res. 2002;62:4491–4498
  38. Poonawala T, Levay-Young BK, Hebbel RP, et al. Opioids heal ischemic wounds in the rat. Wound Repair Regen. 2005;13:165–174
  39. Moss J, Fekete MJ, Lingen M. Morphine induced angiogenesis is blocked by methylnaltrexone. Anesthesiology. 2006;105:A1573
  40. Singleton PA, Lingen MW, Fekete MJ, et al. Methylnaltrexone inhibits opiate and VEGF-induced angiogenesis: role of receptor transactivation. Microvasc Res. 2006;72:3–11

PII: S1084-208X(07)00004-3

doi: 10.1053/j.trap.2007.02.003

Techniques in Regional Anesthesia & Pain Management
Volume 11, Issue 1 , Pages 27-32 , January 2007

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