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
Abstract

Pharmacology of pravadoline: a new analgesic agent.

D R Haubrich, S J Ward, E Baizman, M R Bell, J Bradford, R Ferrari, M Miller, M Perrone, A K Pierson and J K Saelens
Journal of Pharmacology and Experimental Therapeutics November 1990, 255 (2) 511-522;
D R Haubrich
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
S J Ward
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
E Baizman
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
M R Bell
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
J Bradford
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
R Ferrari
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
M Miller
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
M Perrone
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
A K Pierson
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
J K Saelens
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

Pravadoline is a new chemical entity with analgesic activity in humans. This report describes the pharmacology of pravadoline and compares the activity of pravadoline with that of two major classes of analgesics, the opioids and the nonsteroidal anti-inflammatory drugs (NSAIDs). Like the NSAIDs, pravadoline inhibited the synthesis of prostaglandins (PGs) in mouse brain both in vitro (IC50, 4.9 microM) and ex vivo (ED50, 20 mg/kg p.o.) and displayed antinociceptive activity in rodents subjected to a variety of chemical, thermal and mechanical nociceptive stimuli. Administration of pravadoline prevented the writhing response induced by i.p. administration of acetylcholine (ED50, 41 mg/kg p.o.) or PGE2 (ED50, 24 mg/kg p.o.) and prolonged the response latency induced by tail immersion in hot water at a temperature of 55 degrees C (minimum effective dose, 100 mg/kg s.c.). In the rat, treatment with pravadoline prevented acetic acid-induced writhing (ED50, 15 mg/kg p.o.), brewer's yeast-induced hyperalgesia (Randall-Selitto test) (minimum effective dose, 1 mg/kg p.o.), the nociceptive response induced by paw flexion in the adjuvant-arthritic rat (ED50, 41 mg/kg p.o.) and bradykinin-induced head and forepaw flexion (ED50, 78 mg/kg, p.o.). The antinociceptive activity of pravadoline cannot be explained by an opioid mechanism, because pravadoline-induced antinociception was not antagonized by naloxone (1 mg/kg s.c.) and pravadoline did not bind to opioid receptors at concentrations up to 10 microM. However, like the opioid analgesics, pravadoline diminished the electrically induced twitch response of mouse vas deferens preparations, but, in contrast to opioids, this action of pravadoline was not attenuated by naloxone. The possibility is discussed that this effect of pravadoline upon isolated tissues may contribute to its antinociceptive activity. In contrast to NSAIDs, pravadoline was more potent ex vivo as an inhibitor of the formation of PGs in brain vs. stomach. In addition, pravadoline failed to produce gastrointestinal lesions when administered p.o. to rats or mice, and did not possess significant anti-inflammatory activity at antinociceptive doses. Also unlike NSAIDs, pravadoline inhibited rat gastrointestinal transit when administered at doses similar to those which were antinociceptive. The overall pharmacologic profile of pravadoline suggests that the compound may be capable of managing more diverse or more severe pain than is achieved by anti-inflammatory analgesics, without producing side effects commonly associated with either the opioid or the nonopioid analgesics.

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
Vol. 255, Issue 2
1 Nov 1990
  • Table of Contents
  • Index by author
  • Back Matter (PDF)
  • 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.
Pharmacology of pravadoline: a new analgesic agent.
(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
Abstract

Pharmacology of pravadoline: a new analgesic agent.

D R Haubrich, S J Ward, E Baizman, M R Bell, J Bradford, R Ferrari, M Miller, M Perrone, A K Pierson and J K Saelens
Journal of Pharmacology and Experimental Therapeutics November 1, 1990, 255 (2) 511-522;

Citation Manager Formats

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

Share
Abstract

Pharmacology of pravadoline: a new analgesic agent.

D R Haubrich, S J Ward, E Baizman, M R Bell, J Bradford, R Ferrari, M Miller, M Perrone, A K Pierson and J K Saelens
Journal of Pharmacology and Experimental Therapeutics November 1, 1990, 255 (2) 511-522;
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
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

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