Review
Antipruritic treatment with systemic μ-opioid receptor antagonists: A review

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During the past two decades, systemic μ-opioid receptor antagonists (MORA) have been used in the treatment of various forms of chronic pruritus. In a number of case reports, case series, and controlled trials, treatment with MORA has demonstrated considerable antipruritic effects. In double-blind controlled studies, significant antipruritic relief has been achieved by MORA in cholestatic pruritus, chronic urticaria, and atopic dermatitis. In case reports and case series, antipruritic efficacy of MORA has been reported in prurigo nodularis, mycosis fungoides, postburn pruritus, aquagenic pruritus, hydroxyethyl starch-induced pruritus, and pruritus of unknown origin. However, most of the evidence remains anecdotal, the design of these trials varies, and comparison of results is difficult. In this review we aim to present an overview of these reports and to assess the evidence for the antipruritic action of the drugs naloxone, nalmefene, and naltrexone, which are currently in use for the treatment of chronic pruritus of different origins. We will also evaluate recommendations for the use of MORA in daily medical practice.

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Methods

We conducted a literature research for reports on MORA in the treatment of chronic pruritus and itchy conditions. We searched different electronic databases (MEDLINE, Ovid, and DIMDI) using the free text key words “naltrexone,” “nalmefene,” “naloxone,” “opioid receptor antagonist,” “pharmacology,” “pruritus,” “itch,” and their combinations. Search was done without language restriction. Manufacturers of drugs and authors of articles were not contacted. In addition, we included information from

Results

Online search yielded a total of 318 reports from 1979 to 2009 containing the key words mentioned above. We included 58 clinical articles mainly reporting on chronic pruritus and some examples in acute pruritus. Case reports and studies on morphine-induced pruritus were excluded. The main topics addressed in these studies were the pharmacology of opioid receptor antagonists, their neuronal mechanism, and their clinical antipruritic potency.

References (80)

  • G. Heyer et al.

    Opiate and H1 antagonist effects on histamine induced pruritus and allokinesis

    Pain

    (1997)
  • T. Yamaguchi et al.

    Itch-associated response induced by intradermal serotonin through 5-HT2 receptors in mice

    Neurosci Res

    (1999)
  • A.G. Dawn et al.

    Butorphanol for treatment of intractable pruritus

    J Am Acad Dermatol

    (2006)
  • N.V. Bergasa et al.

    Oral nalmefene therapy reduces scratching activity due to the pruritus of cholestasis: a controlled study

    J Am Acad Dermatol

    (1999)
  • F.H. Wolfhagen et al.

    Oral naltrexone treatment for cholestatic pruritus: a double-blind, placebo-controlled study

    Gastroenterology

    (1997)
  • N.V. Bergasa et al.

    A controlled trial of naloxone infusions for the pruritus of chronic cholestasis

    Gastroenterology

    (1992)
  • R. Terg et al.

    Efficacy and safety of oral naltrexone treatment for pruritus of cholestasis, a crossover, double blind, placebo controlled study

    J Hepatol

    (2002)
  • D. Banerji et al.

    Controlled antipruritic trial of nalmefene in chronic urticaria and atopic dermatitis

    J Allergy Clin Immunol

    (1988)
  • L. LaSalle et al.

    Naltrexone for the management of post-burn pruritus: a preliminary report

    Burns

    (2008)
  • J. Moss et al.

    Development of peripheral opioid antagonists' new insights into opioid effects

    Mayo Clin Proc

    (2008)
  • C.S. Yuan et al.

    Efficacy of orally administered methylnaltrexone in decreasing subjective effects after intravenous morphine

    Drug Alcohol Depend

    (1998)
  • S. Commiskey et al.

    Butorphanol: effects of a prototypical agonist-antagonist analgesic on kappa-opioid receptors

    J Pharmacol Sci

    (2005)
  • E. Dunteman et al.

    Transnasal butorphanol for the treatment of opioid-induced pruritus unresponsive to antihistamines

    J Pain Symptom Manage

    (1996)
  • A. Ikoma et al.

    The neurobiology of itch

    Nat Rev Neurosci

    (2006)
  • J.D. Friedman et al.

    Opioid antagonists in the treatment of opioid-induced constipation and pruritus

    Ann Pharmacother

    (2001)
  • S.H. Ngai et al.

    Pharmacokinetics of naloxone in rats and man

    Anesthesiology

    (1976)
  • D.R. Jasinski et al.

    The human pharmacology and abuse potential of n-allylnoroxymorphone (Naloxone)

    J Pharmacol Exp Ther

    (1967)
  • W.R. Martin et al.

    Naltrexone, an antagonist for the treatment of heroin dependence

    Arch Gen Psychiatry

    (1973)
  • M.C. Lee et al.

    Duration of occupancy of opiate receptors by naltrexone

    J Nucl Med

    (1988)
  • J.P. Gonzalez et al.

    Naltrexone: a review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in the management of opioid dependence

    Drugs

    (1988)
  • K. Verebey et al.

    Naltrexone: disposition, metabolism and effects after acute and chronic dosing

    Clin Pharmacol Ther

    (1976)
  • M.C. Meyer et al.

    Bioequivalence, dose proportionality and pharmacokinetics of naltrexone after oral administration

    J Clin Psychiatry

    (1984)
  • E.J. Cone et al.

    The urinary excretion profile of naltrexone and metabolites in man

    Drug Metab Dispos

    (1974)
  • J. Volavka et al.

    Hormonal and other effects of naltrexone in normal men

    Adv Exp Med Biol

    (1979)
  • E.F. Hahn et al.

    Narcotic antagonist, 4carbon-6 derivates of Nsubstituted noroxymorphones as narcotic antagonists

    J Med Chem

    (1975)
  • S. Kim et al.

    Longer occupancy of opioid receptors by nalmefene compared to naloxone as measured in vivo by dual-detector systems

    J Nucl Med

    (1997)
  • T.J. Gal et al.

    Prolonged blockade of opioid effect with oral nalmefene

    Clin Pharmacol Ther

    (1986)
  • G.R. Matzke et al.

    The effect of renal insufficiency and hemodialysis on the pharmacokinetics of nalmefene

    J Clin Pharmacol

    (1996)
  • M.E. Michel et al.

    Binding of a new opiate antagonist, nalmefene, to rat brain membranes

    Methods Find Exp Clin Pharmacol

    (1985)
  • A. Chumpa

    Nalmefene hydrochloride

    Pediatr Emerg Care

    (1999)
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    Funding sources: None.

    Conflicts of interest: None declared.

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