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Targeting Itch with Ligands Selective for κ Opioid Receptors

  • Chapter
Book cover Pharmacology of Itch

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 226))

Abstract

Several chemically diverse pruritogens, including bombesin, compound 48/80, norbinaltorphimine, and 5′-GNTI, cause rodents to scratch excessively in a stable, uniform manner and consequently provide convenient animal models of itch against which potential antipruritics may be evaluated, structure–activity relationships established, and the nature of spontaneous, repetitive behavior itself analyzed. Decreasing the number of scratching bouts in these apparently simple models has been the requisite first step in the progress of kappa opioid agonists such as nalbuphine, asimadoline, and CR845 toward clinical testing as antipruritics. Nalfurafine is the prime example of a kappa agonist spanning the developmental divide between scratching mice models and commercialization within 10 years. Patients undergoing hemodialysis and suffering from the itching associated with uremic pruritus, and potentially those inflicted with atopic dermatitis, are the beneficiaries.

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Abbreviations

A50 (antiscratch-50):

The dose of test compound that antagonizes pruritogen-induced scratching by 50 % on a scale that ranges from vehicle (control) value to 100 %

ACTH:

Adrenocorticotropic hormone

ADL 10–0101:

N-Methyl-N-[(1S)-(1-phenyl-2-pyrrolidinyl)ethyl]-2-methane-sulfonamidylphenylacetamide methanesulfonate

EKC:

Ethylketocyclazocine

GR 94839:

4-Acetyl-1-(3,4-dichlorophenyl)acetyl-2-[(3-hydroxy-1-pyrrolidinyl)methyl]piperazine

GRP:

Gastrin-releasing peptide

ICI 204,448:

(RS)-[3-[1-[[3,4-Dichlorophenyl)acetyl]methylamino]-2-(1-pyrrolidinyl)ethyl]phenoxy]acetic acid

icv:

Intracerebroventricular

JDTic:

(3R)-7-Hydroxy-N-[(1S)-1-{[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl}-2-methylpropyl]-1,2,3,4-tetrahydro-3-isoquinoline-carboxamide

JNJ 10191584:

1-[(5-Chloro-1H-benzimidazol-2-yl)carbonyl]-4-methylpiperazine

JNJ 39758979:

(R)-4-(3-Amino-pyrrolidin-1-yl)-6-isopropyl-pyrimidin-2-ylamine

KOP:

Kappa opioid

McN-A-343:

4-(m-Chlorophenyl-carbamoyloxy)-2-butynyltrimethylammonium chloride

norBNI:

Norbinaltorphimine

ODT8-SS:

des-AA1,2,4,5,12,13[D-Trp8]somatostatin

RC-3095:

[D-Tpi6 Leu13ψ(CH2NH)Leu14]bombesin (6–14)

U-50,488:

trans-(±)-3,4-Dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzeneacetamide

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Acknowledgment

Work carried out in the Cowan lab was funded, in part, by DA013429 and T32DA 007237 from the National Institute on Drug Abuse.

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Author notes

  1. George B. Kehner

    Present address: Shire Pharmaceuticals, 725 Chesterbrook Blvd., Chesterbrook, PA, 19087, USA

  2. Saadet Inan

    Present address: , 10767 Pelle Circle, Philadelphia, PA, 19154, USA

Authors and Affiliations

  1. Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, 19140, USA

    Alan Cowan, George B. Kehner & Saadet Inan

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

    Alan Cowan

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  1. Alan Cowan
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  2. George B. Kehner
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  3. Saadet Inan
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Correspondence to Alan Cowan .

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Editors and Affiliations

  1. Department of Pharmacology Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, Pennsylvania, USA

    Alan Cowan

  2. Department of Dermatology, Temple University School of Medicine, Philadephia, Pennsylvania, USA

    Gil Yosipovitch

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Cowan, A., Kehner, G.B., Inan, S. (2015). Targeting Itch with Ligands Selective for κ Opioid Receptors. In: Cowan, A., Yosipovitch, G. (eds) Pharmacology of Itch. Handbook of Experimental Pharmacology, vol 226. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-44605-8_16

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