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
Research ArticleDrug Discovery and Translational Medicine

Analgesic Properties of a Peripherally Acting and GalR2 Receptor–Preferring Galanin Analog in Inflammatory, Neuropathic, and Acute Pain Models

Cameron S. Metcalf, Brian D. Klein, Daniel R. McDougle, Liuyin Zhang, Misty D. Smith, Grzegorz Bulaj and H. Steve White
Journal of Pharmacology and Experimental Therapeutics January 2015, 352 (1) 185-193; DOI: https://doi.org/10.1124/jpet.114.219063
Cameron S. Metcalf
Neuroadjuvants, Inc., Salt Lake City, Utah (C.S.M., B.D.K., D.R.M.); and Departments of Pharmacology and Toxicology (B.D.K., M.D.S., H.S.W.) and Medicinal Chemistry (L.Z., G.B.), College of Pharmacy, University of Utah, Salt Lake City, Utah
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Brian D. Klein
Neuroadjuvants, Inc., Salt Lake City, Utah (C.S.M., B.D.K., D.R.M.); and Departments of Pharmacology and Toxicology (B.D.K., M.D.S., H.S.W.) and Medicinal Chemistry (L.Z., G.B.), College of Pharmacy, University of Utah, Salt Lake City, Utah
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Daniel R. McDougle
Neuroadjuvants, Inc., Salt Lake City, Utah (C.S.M., B.D.K., D.R.M.); and Departments of Pharmacology and Toxicology (B.D.K., M.D.S., H.S.W.) and Medicinal Chemistry (L.Z., G.B.), College of Pharmacy, University of Utah, Salt Lake City, Utah
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Liuyin Zhang
Neuroadjuvants, Inc., Salt Lake City, Utah (C.S.M., B.D.K., D.R.M.); and Departments of Pharmacology and Toxicology (B.D.K., M.D.S., H.S.W.) and Medicinal Chemistry (L.Z., G.B.), College of Pharmacy, University of Utah, Salt Lake City, Utah
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Misty D. Smith
Neuroadjuvants, Inc., Salt Lake City, Utah (C.S.M., B.D.K., D.R.M.); and Departments of Pharmacology and Toxicology (B.D.K., M.D.S., H.S.W.) and Medicinal Chemistry (L.Z., G.B.), College of Pharmacy, University of Utah, Salt Lake City, Utah
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Grzegorz Bulaj
Neuroadjuvants, Inc., Salt Lake City, Utah (C.S.M., B.D.K., D.R.M.); and Departments of Pharmacology and Toxicology (B.D.K., M.D.S., H.S.W.) and Medicinal Chemistry (L.Z., G.B.), College of Pharmacy, University of Utah, Salt Lake City, Utah
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
H. Steve White
Neuroadjuvants, Inc., Salt Lake City, Utah (C.S.M., B.D.K., D.R.M.); and Departments of Pharmacology and Toxicology (B.D.K., M.D.S., H.S.W.) and Medicinal Chemistry (L.Z., G.B.), College of Pharmacy, University of Utah, Salt Lake City, Utah
  • 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 are ongoing efforts to develop pain therapeutics with novel mechanisms of action that avoid common side effects associated with other analgesics. The anticonvulsant neuropeptide galanin is a potent regulator of neuronal excitability and has a well established role in pain modulation, making it a potential target for novel therapies. Our previous efforts focused on improving blood-brain-barrier penetration and enhancing the metabolic stability of galanin analogs to protect against seizures. More recently, we designed peripherally acting galanin analogs that reduce pain-related behaviors by acting in the periphery and exhibit preferential binding toward galanin receptor (GalR)2 over GalR1. In this study, we report preclinical studies of a monodisperse oligoethylene glycol–containing galanin analog, NAX 409-9 (previously reported as GalR2-dPEG24), in rodent analgesic and safety models. Results obtained with NAX 409-9 in these tests were compared with the representative analgesics gabapentin, ibuprofen, acetylsalicylic acid, acetaminophen, and morphine. In mice that received intraplantar carrageenan, NAX 409-9 increased paw withdrawal latency with an ED50 of 6.6 mg/kg i.p. NAX 409-9 also increased the paw withdrawal threshold to mechanical stimulation following partial sciatic nerve ligation in rats (2 mg/kg). Conversely, NAX 409-9 had no effect in the tail flick or hot plate assays (up to 24 mg/kg). Importantly, NAX 409-9 did not negatively affect gastrointestinal motility (4–20 mg/kg), respiratory rate (40–80 mg/kg), or bleed time (20 mg/kg). These studies illustrate that this nonbrain-penetrating galanin analog reduces pain behaviors in several models and does not produce some of the dose-limiting toxicities associated with other analgesics.

Footnotes

    • Received August 7, 2014.
    • Accepted October 24, 2014.
  • This work was supported in part by the National Institutes of Health National Institute of Neurological Disorders and Stroke [Grant R21-NS059669 to G.B. and H.S.W.].

  • G.B. and H.S.W. are scientific cofounders of Neuroadjuvants, Inc.

  • Some of the data presented in this work has been previously presented as follows: Metcalf CS, Klein BD, McDougle DR, Bulaj G, and White HS (2012) Antinociceptive effects of novel GalR2-specific analogs. Experimental Biology 2012; 2012 Apr 21–25; San Diego, CA. American Society for Pharmacology and Experimental Therapeutics; and Metcalf CS, Klein BD, McDougle DR, Zhang L, Smith MD, Bulaj G, and White HS (2013) Development of peripherally-acting, GalR2-preferring galanin analogs for the treatment of pain. Galanin SFN Pre-Meeting 2013; 2013 Nov 8–9; San Diego, CA.

  • dx.doi.org/10.1124/jpet.114.219063.

  • Copyright © 2014 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: 352 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 352, Issue 1
1 Jan 2015
  • 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.
Analgesic Properties of a Peripherally Acting and GalR2 Receptor–Preferring Galanin Analog in Inflammatory, Neuropathic, and Acute Pain Models
(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

Analgesic Properties of a GalR2 Receptor-Preferring Analog

Cameron S. Metcalf, Brian D. Klein, Daniel R. McDougle, Liuyin Zhang, Misty D. Smith, Grzegorz Bulaj and H. Steve White
Journal of Pharmacology and Experimental Therapeutics January 1, 2015, 352 (1) 185-193; DOI: https://doi.org/10.1124/jpet.114.219063

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

Analgesic Properties of a GalR2 Receptor-Preferring Analog

Cameron S. Metcalf, Brian D. Klein, Daniel R. McDougle, Liuyin Zhang, Misty D. Smith, Grzegorz Bulaj and H. Steve White
Journal of Pharmacology and Experimental Therapeutics January 1, 2015, 352 (1) 185-193; DOI: https://doi.org/10.1124/jpet.114.219063
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
    • Materials and Methods
    • Results
    • Discussion
    • Authorship Contributions
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • C. butyricum Alleviates Bone Loss after Bariatric Surgery
  • Antimuscarinic Effects of Mirabegron
  • Apigenin Relieves Hyperlipidemia
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 © 2021 by the American Society for Pharmacology and Experimental Therapeutics