Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Comparison of morphine, oxycodone and the biased MOR agonist SR-17018 for tolerance and efficacy in mouse models of pain

Fani Pantouli, Travis W. Grim, Cullen L. Schmid, Agnes Acevedo-Canabal, Nicole M. Kennedy, Thomas D. Bannister, View ORCID ProfileLaura M. Bohn
doi: https://doi.org/10.1101/2020.10.16.341776
Fani Pantouli
1Departments of Molecular Medicine and Neuroscience, The Scripps Research Institute, Jupiter, FL
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Travis W. Grim
1Departments of Molecular Medicine and Neuroscience, The Scripps Research Institute, Jupiter, FL
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Cullen L. Schmid
1Departments of Molecular Medicine and Neuroscience, The Scripps Research Institute, Jupiter, FL
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Agnes Acevedo-Canabal
1Departments of Molecular Medicine and Neuroscience, The Scripps Research Institute, Jupiter, FL
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nicole M. Kennedy
2Molecular Medicine and Chemistry, The Scripps Research Institute, Jupiter, FL
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Thomas D. Bannister
2Molecular Medicine and Chemistry, The Scripps Research Institute, Jupiter, FL
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Laura M. Bohn
1Departments of Molecular Medicine and Neuroscience, The Scripps Research Institute, Jupiter, FL
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Laura M. Bohn
  • For correspondence: LBohn@scripps.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

The mu opioid receptor-selective agonist, SR-17018, preferentially activates GTPγS binding over βarrestin2 recruitment in cellular assays. In mice, SR-17018 stimulates GTPγS binding in brainstem and produces antinociception with potencies similar to morphine. However, it produces much less respiratory suppression and mice do not develop antinociceptive tolerance in the hot plate assay upon repeated dosing. Herein we evaluate the effects of acute and repeated dosing of SR-17018, oxycodone and morphine in additional models of pain-related behaviors. In the mouse warm water tail immersion assay, an assessment of spinal reflex to thermal nociception, repeated administration of SR-17018 produces tolerance as does morphine and oxycodone. SR-17018 retains efficacy in a formalin-induced inflammatory pain model upon repeated dosing, while oxycodone does not. In a chemotherapeutic-induced neuropathy pain model SR-17018 is more potent and efficacious than morphine or oxycodone, moreover, this efficacy is retained upon repeated dosing of SR-17018. These findings demonstrate that, with the exception of the tail flick test, SR-17018 retains efficacy upon chronic treatment across several pain models.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted October 16, 2020.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Comparison of morphine, oxycodone and the biased MOR agonist SR-17018 for tolerance and efficacy in mouse models of pain
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Comparison of morphine, oxycodone and the biased MOR agonist SR-17018 for tolerance and efficacy in mouse models of pain
Fani Pantouli, Travis W. Grim, Cullen L. Schmid, Agnes Acevedo-Canabal, Nicole M. Kennedy, Thomas D. Bannister, Laura M. Bohn
bioRxiv 2020.10.16.341776; doi: https://doi.org/10.1101/2020.10.16.341776
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Comparison of morphine, oxycodone and the biased MOR agonist SR-17018 for tolerance and efficacy in mouse models of pain
Fani Pantouli, Travis W. Grim, Cullen L. Schmid, Agnes Acevedo-Canabal, Nicole M. Kennedy, Thomas D. Bannister, Laura M. Bohn
bioRxiv 2020.10.16.341776; doi: https://doi.org/10.1101/2020.10.16.341776

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Pharmacology and Toxicology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4688)
  • Biochemistry (10371)
  • Bioengineering (7693)
  • Bioinformatics (26367)
  • Biophysics (13547)
  • Cancer Biology (10719)
  • Cell Biology (15459)
  • Clinical Trials (138)
  • Developmental Biology (8509)
  • Ecology (12841)
  • Epidemiology (2067)
  • Evolutionary Biology (16884)
  • Genetics (11412)
  • Genomics (15491)
  • Immunology (10637)
  • Microbiology (25246)
  • Molecular Biology (10234)
  • Neuroscience (54575)
  • Paleontology (402)
  • Pathology (1671)
  • Pharmacology and Toxicology (2899)
  • Physiology (4353)
  • Plant Biology (9263)
  • Scientific Communication and Education (1588)
  • Synthetic Biology (2558)
  • Systems Biology (6788)
  • Zoology (1470)