Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • 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
  • 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
    • 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
  • Visit jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Review ArticleMinireview

Strategies for Developing κ Opioid Receptor Agonists for the Treatment of Pain with Fewer Side Effects

Kelly F. Paton, Diana V. Atigari, Sophia Kaska, Thomas Prisinzano and Bronwyn M. Kivell
Journal of Pharmacology and Experimental Therapeutics November 2020, 375 (2) 332-348; DOI: https://doi.org/10.1124/jpet.120.000134
Kelly F. Paton
School of Biological Sciences, Centre for Biodiscovery, Victoria University of Wellington, Wellington, New Zealand (K.P., D.V.A., B.M.K.) and Department of Pharmaceutical Sciences, University of Kentucky, Lexington, Kentucky (S.K., T.P.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Diana V. Atigari
School of Biological Sciences, Centre for Biodiscovery, Victoria University of Wellington, Wellington, New Zealand (K.P., D.V.A., B.M.K.) and Department of Pharmaceutical Sciences, University of Kentucky, Lexington, Kentucky (S.K., T.P.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sophia Kaska
School of Biological Sciences, Centre for Biodiscovery, Victoria University of Wellington, Wellington, New Zealand (K.P., D.V.A., B.M.K.) and Department of Pharmaceutical Sciences, University of Kentucky, Lexington, Kentucky (S.K., T.P.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Thomas Prisinzano
School of Biological Sciences, Centre for Biodiscovery, Victoria University of Wellington, Wellington, New Zealand (K.P., D.V.A., B.M.K.) and Department of Pharmaceutical Sciences, University of Kentucky, Lexington, Kentucky (S.K., T.P.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bronwyn M. Kivell
School of Biological Sciences, Centre for Biodiscovery, Victoria University of Wellington, Wellington, New Zealand (K.P., D.V.A., B.M.K.) and Department of Pharmaceutical Sciences, University of Kentucky, Lexington, Kentucky (S.K., T.P.)
  • 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

There is significant need to find effective, nonaddictive pain medications. κ Opioid receptor (KOPr) agonists have been studied for decades but have recently received increased attention because of their analgesic effects and lack of abuse potential. However, a range of side effects have limited the clinical development of these drugs. There are several strategies currently used to develop safer and more effective KOPr agonists. These strategies include identifying G-protein–biased agonists, developing peripherally restricted KOPr agonists without centrally mediated side effects, and developing mixed opioid agonists, which target multiple receptors at specific ratios to balance side-effect profiles and reduce tolerance. Here, we review the latest developments in research related to KOPr agonists for the treatment of pain.

SIGNIFICANCE STATEMENT This review discusses strategies for developing safer κ opioid receptor (KOPr) agonists with therapeutic potential for the treatment of pain. Although one strategy is to modify selective KOPr agonists to create peripherally restricted or G-protein–biased structures, another approach is to combine KOPr agonists with μ, δ, or nociceptin opioid receptor activation to obtain mixed opioid receptor agonists, therefore negating the adverse effects and retaining the therapeutic effect.

Footnotes

    • Received May 28, 2020.
    • Accepted August 27, 2020.
  • ↵1 K.F.P. and D.V.A. contributed equally to this work.

  • This work was supported by the Health Research Council of New Zealand, B.M.K. [Grant 16/646] and National Institutes of Health National Institute on Drug Abuse [Grant RO1: DA018151] (to T.E.P.). K.F.P. and D.V.A. each received a doctoral scholarship from Victoria University of Wellington.

  • https://doi.org/10.1124/jpet.120.000134.

  • Copyright © 2020 by 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: 375 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 375, Issue 2
1 Nov 2020
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Editorial Board (PDF)
  • Front Matter (PDF)
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.
Strategies for Developing κ Opioid Receptor Agonists for the Treatment of Pain with Fewer Side 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
Review ArticleMinireview

Strategies for Developing Safer κ Opioid Receptor Agonists

Kelly F. Paton, Diana V. Atigari, Sophia Kaska, Thomas Prisinzano and Bronwyn M. Kivell
Journal of Pharmacology and Experimental Therapeutics November 1, 2020, 375 (2) 332-348; DOI: https://doi.org/10.1124/jpet.120.000134

Citation Manager Formats

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

Strategies for Developing Safer κ Opioid Receptor Agonists

Kelly F. Paton, Diana V. Atigari, Sophia Kaska, Thomas Prisinzano and Bronwyn M. Kivell
Journal of Pharmacology and Experimental Therapeutics November 1, 2020, 375 (2) 332-348; DOI: https://doi.org/10.1124/jpet.120.000134
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • κ Opioid Receptor Signaling and the Role in Pain
    • Traditional Arylacetamide κ Opioid Receptor Agonists
    • Strategies to Develop κ Opioid Receptor Agonists with Reduced Side Effects
    • G-Protein–Biased κ Opioid Receptor Agonists
    • Peripherally Restricted κ Opioid Receptor Agonists
    • Mixed κ Opioid Receptor Agonists
    • Conclusions
    • Authorship Contributions
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Stem Cells Therapies in AD
  • Targeting the Protective Arm of the Renin-Angiotensin System
  • Regulating RNA in Treating IBD and Colon Cancer
Show more Minireview

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 © 2021 by the American Society for Pharmacology and Experimental Therapeutics