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Kappa-Opioid Antagonists as Pruritogenic Agents

  • Chapter
Opiate Receptors and Antagonists

Part of the book series: Contemporary Neuroscience ((CNEURO))

Abstract

Norbinaltorphimine (norBNI), the prototype kappa-opioid receptor antagonist, N-benzylnorBNI, and 5′-guanidinonaltrindole (GNTI) precipitate stereotyped scratching after subcutaneous injection behind the neck of Swiss-Webster mice. The intensity of the behavioral activation and its repetitive nature represent one of the most arresting sights in preclinical psychopharmacology. The rank order for both potency and efficacy was GNTI > norBNI > N-benzylnorBNI. Although nalfurafine, the clinically tested kappa-opioid receptor agonist, decreased the incidence of GNTI-induced compulsive scratching in a dose-related manner, it is likely that this antagonism is mediated by mechanisms additional to a possible direct interaction with kappa receptors.

The robust syndrome will be of interest to basic scientists as a compelling behavior in its own right, as well as providing an experimental model for potential drug discovery in psycho- and dermatopharmacology.

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Author information

Authors and Affiliations

  1. Department of Pharmacology, Temple University School of Medicine, North Broad Street, 3420, Philadelphia, PA, 19140

    Alan Cowan

  2. Department of Pharmacology and Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA, 19140

    Saadet Inan

Authors
  1. Alan Cowan
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  2. Saadet Inan
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Editor information

Editors and Affiliations

  1. Life Sciences/Toxicology, Alkermes, Inc., Cambridge, MA, 02139, USA

    Reginald L. Dean III

  2. Department of Pharmacology, College of Osteopathic Medicine, University of New England, Biddleford, ME, 04005, USA

    Edward J. Bilsky

  3. Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, 23298, USA

    S. Stevens Negus

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Cowan, A., Inan, S. (2009). Kappa-Opioid Antagonists as Pruritogenic Agents. In: Dean, R.L., Bilsky, E.J., Negus, S.S. (eds) Opiate Receptors and Antagonists. Contemporary Neuroscience. Humana Press. https://doi.org/10.1007/978-1-59745-197-0_28

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