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 ArticleDrug Discovery and Translational Medicine

A Novel Maintenance Therapeutic for Opioid Use Disorder

Beth Youngblood, Kevin Li, Donald R. Gehlert, Julio C. Medina and Neil Schwartz
Journal of Pharmacology and Experimental Therapeutics August 2021, 378 (2) 133-145; DOI: https://doi.org/10.1124/jpet.120.000214
Beth Youngblood
Epiodyne Inc., San Francisco, California (B.Y., D.R.G., J.C.M., N.S.) and R2M Pharma Inc., South San Francisco, California (K.L., J.C.M.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kevin Li
Epiodyne Inc., San Francisco, California (B.Y., D.R.G., J.C.M., N.S.) and R2M Pharma Inc., South San Francisco, California (K.L., J.C.M.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Donald R. Gehlert
Epiodyne Inc., San Francisco, California (B.Y., D.R.G., J.C.M., N.S.) and R2M Pharma Inc., South San Francisco, California (K.L., J.C.M.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Julio C. Medina
Epiodyne Inc., San Francisco, California (B.Y., D.R.G., J.C.M., N.S.) and R2M Pharma Inc., South San Francisco, California (K.L., J.C.M.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Neil Schwartz
Epiodyne Inc., San Francisco, California (B.Y., D.R.G., J.C.M., N.S.) and R2M Pharma Inc., South San Francisco, California (K.L., J.C.M.)
  • 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 + SI
  • PDF
Loading

Abstract

Opioid use disorder (OUD) is a major socioeconomic burden. An ideal OUD pharmacotherapy will mitigate the suffering associated with opioid-withdrawal, inhibit the effects of high efficacy opioids, and minimize opioid-cravings while being safe and accessible to a diverse patient population. Although current OUD pharmacotherapies inhibit the euphoric effects of opioids of abuse, the extent to which they safely alleviate withdrawal and opioid-cravings corresponds with their intrinsic µ opioid receptor (MOR) efficacy. In addition to inhibiting the euphoric effects of opioids of abuse, the medium efficacy MOR agonist buprenorphine alleviates withdrawal and opioid-cravings, but its intrinsic MOR efficacy is sufficient such that its utility is limited by abuse and safety liabilities. Although the MOR antagonist naltrexone minimizes euphoria and has no abuse liability, it exacerbates suffering associated with withdrawal and opioid cravings. Therefore, a therapeutic with intrinsic MOR activity between the partial agonist (buprenorphine) and the antagonist (naltrexone) would strike a balance between the benefits and liabilities of these two therapeutics. To address this need, we derived RM1490, an MOR agonist based on a nonmorphinan scaffold that exhibits approximately half the intrinsic MOR efficacy of buprenorphine. In a series of preclinical assays, we compared RM1490 with buprenorphine and naltrexone at doses that achieve therapeutic levels of central nervous system MOR occupancy. RM1490 exhibited a behavioral profile consistent with reduced reward, dependence, and precipitated withdrawal liabilities. RM1490 was also more effective than buprenorphine at reversing the respiratory depressant effects of fentanyl and did not suppress respiration when combined with diazepam.

SIGNIFICANCE STATEMENT In preclinical studies, RM1490 has a physiological and behavioral profile suitable for opioid use disorder maintenance therapy.

Footnotes

    • Received July 13, 2020.
    • Accepted May 17, 2021.
  • This work was supported by National Institutes of Health National Institute of Drug Abuse [Grant 1UG3DA049598-01].

  • B.Y., D.R.G., J.C.M., and N.S. are employees of and stockholders in Epiodyne Inc. J.C.M. and K.L. are also stockholders and employees of R2M Pharma Inc.

  • https://doi.org/10.1124/jpet.120.000214.

  • ↵Embedded ImageThis article has supplemental material available at jpet.aspetjournals.org.

  • Copyright © 2021 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: 378 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 378, Issue 2
1 Aug 2021
  • 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.
A Novel Maintenance Therapeutic for Opioid Use Disorder
(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 ArticleDrug Discovery and Translational Medicine

A Novel Opioid Use Disorder Treatment

Beth Youngblood, Kevin Li, Donald R. Gehlert, Julio C. Medina and Neil Schwartz
Journal of Pharmacology and Experimental Therapeutics August 1, 2021, 378 (2) 133-145; DOI: https://doi.org/10.1124/jpet.120.000214

Citation Manager Formats

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

Share
Research ArticleDrug Discovery and Translational Medicine

A Novel Opioid Use Disorder Treatment

Beth Youngblood, Kevin Li, Donald R. Gehlert, Julio C. Medina and Neil Schwartz
Journal of Pharmacology and Experimental Therapeutics August 1, 2021, 378 (2) 133-145; DOI: https://doi.org/10.1124/jpet.120.000214
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
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Authorship Contributions:
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • SGS742 and Treatment of GHB Overdoses
  • Fate determination role of erythropoietin and romiplostim
  • Pharmacology of Antifentanyl mAb with Naloxone in Rats
Show more Drug Discovery and Translational Medicine

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