Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Journal of Pharmacology and Experimental Therapeutics
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Journal of Pharmacology and Experimental Therapeutics

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleNEUROPHARMACOLOGY

Nonopioid Actions of U50,488 Enantiomers Contribute to Their Peripheral Cutaneous Antinociceptive Effects

S. K. Joshi and G. F. Gebhart
Journal of Pharmacology and Experimental Therapeutics June 2003, 305 (3) 919-924; DOI: https://doi.org/10.1124/jpet.103.049023
S. K. Joshi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
G. F. Gebhart
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

The ability of arylacetamide κ-opioid receptor agonists (κ-ORAs) to block sodium channels by a nonopioid mechanism has been previously documented. The present experiments were undertaken to test whether two enantiomers of the arylacetamide κ-ORA (trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzeneacetamide (U50,488), (+)-(1R,2R)-U50,488 and (–)-(1S,2S)-U50,488, are antinociceptive in the formalin model by a peripheral, nonopioid receptor-mediated mechanism. Although both enantiomers have been previously shown to block sodium channels with comparable potencies, only (–)-(1S,2S)-U50,488 has activity at the κ-opioid receptor (KOR). In the formalin test, intrapaw administration of U50,488 enantiomers as well as lidocaine exhibited significant dose-related attenuation of formalin-induced flinching behavior. The rank order of potency of the drugs tested was (–)-(1S,2S)-U50,488 > (+)-(1R,2R)-U50,488 > lidocaine. The antinociception produced by lower doses of (–)-(1S,2S)-U50,488 was blocked by intrapaw nor-binaltorphimine as well as by antisense knockdown of the KOR. Such pretreatments, however, did not block the antinociception produced by (+)-(1R,2R) U50,488, lidocaine, or higher doses of (–)-(1S,2S)-U50,488. These data suggest that the sodium channel blocking effects of U50,488 and similar κ-ORAs can contribute to their peripheral antinociceptive actions.

Footnotes

  • This study was supported by Grant NS19912.

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

  • DOI: 10.1124/jpet.103.049023.

  • ABBREVIATIONS: ORA, opioid receptor agonist; KOR, κ-opioid receptor; nor-BNI, nor-binaltorphimine; ODN, oligodeoxynucleotide; U50,488, (trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzeneacetamide; U69,593, (5α,7α,8β)-(–)-N-methyl-N-(7-(1-pyrrolidinyl)-1-oxaspiro (4,5)dec-8-yl) benzeneacetamide; PD 129,289, [5R-(5α,7α,8β)]-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4.5]dec-8-yl]-4-benzofuranacetamide Hcl; PD 129,290, [5S-(5α,7α,8β)]-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4.5]dec-8-yl]-4-benzofuranacetamide Hcl; EMD 61,753, (N-methyl-N-[(1S)-1-phenyl)-2-(13S))-3-hydroxypyrrolidine-1-yl)-ethyl]-2,2-diphenylacetamide HCl.

    • Received January 15, 2003.
    • Accepted February 25, 2003.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

JPET articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Journal of Pharmacology and Experimental Therapeutics: 305 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 305, Issue 3
1 Jun 2003
  • Table of Contents
  • About the Cover
  • Index by author
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Journal of Pharmacology and Experimental Therapeutics article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Nonopioid Actions of U50,488 Enantiomers Contribute to Their Peripheral Cutaneous Antinociceptive Effects
(Your Name) has forwarded a page to you from Journal of Pharmacology and Experimental Therapeutics
(Your Name) thought you would be interested in this article in Journal of Pharmacology and Experimental Therapeutics.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleNEUROPHARMACOLOGY

Nonopioid Actions of U50,488 Enantiomers Contribute to Their Peripheral Cutaneous Antinociceptive Effects

S. K. Joshi and G. F. Gebhart
Journal of Pharmacology and Experimental Therapeutics June 1, 2003, 305 (3) 919-924; DOI: https://doi.org/10.1124/jpet.103.049023

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleNEUROPHARMACOLOGY

Nonopioid Actions of U50,488 Enantiomers Contribute to Their Peripheral Cutaneous Antinociceptive Effects

S. K. Joshi and G. F. Gebhart
Journal of Pharmacology and Experimental Therapeutics June 1, 2003, 305 (3) 919-924; DOI: https://doi.org/10.1124/jpet.103.049023
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Iclepertin (BI 425809) in schizophrenia-related models
  • D1 agonist vs. methylphenidate on PFC working memory
  • Obesity Thwarts Preconditioning in TBI
Show more Neuropharmacology

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About JPET
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0103 (Online)

Copyright © 2022 by the American Society for Pharmacology and Experimental Therapeutics