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 ArticleArticle

Selective Cyclooxygenase-2 Inhibition by Nimesulide in Man

Louise Cullen, Linda Kelly, Shane O. Connor and Desmond J. Fitzgerald
Journal of Pharmacology and Experimental Therapeutics November 1998, 287 (2) 578-582;
Louise Cullen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Linda Kelly
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shane O. Connor
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Desmond J. Fitzgerald
  • 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

Prostaglandins are generated through two isoforms of the enzyme cyclooxygenase, the constitutively expressed cyclooxygenase (Cox)-1 and Cox-2, which is induced at sites of inflammation. Selective inhibition of Cox-2 is desirable as this may avoid the gastropathy and platelet inhibition seen with nonselective agents. Moreover, these agents will allow us to examine the relative contribution of the two isoforms to prostaglandin formation in man. We examined the activity of nimesulide, a Cox-2 selective nonsteroidal antiinflammatory drug, in vitro against purified enzymes and in vivo in man. Nimesulide 100 mg twice daily or aspirin 300 mg three times daily were administered randomly for 14 days to 20 subjects complaining of musculoskeletal pain. Serum thromboxane B2 was determined as an index of Cox-1 activity and endotoxin-induced prostaglandin E2 formation in whole blood as an index of Cox-2 activity. Urinary excretion of prostaglandin metabolites was determined by GC/MS. Nimesulide was highly selective against ovine Cox-2, so that at concentrations attained in vivo, it had no effect on Cox-1 but completely suppressed Cox-2. Aspirin markedly inhibited serum thromboxane B2 (181.92 ± 19.77 to 2.83 ± 0.96 ng/ml, P < .002), whereas nimesulide had very little effect (207.53 ± 47.30 to 181.15 ± 54.59 ng/ml). In contrast, nimesulide suppresses endotoxin-induced prostaglandin E2formation (35.03 ± 8.73 to 2.62 ± 0.95 ng/ml, P = .002). As expected, aspirin reduced TX metabolite excretion, whereas nimesulide had no significant effect. In contrast, both compounds suppressed PGI2 formation to the same extent. The findings suggest that TX is largely Cox-1 derived. Moreover, Cox-2 is expressed in man and generates prostaglandin I2.

Footnotes

  • Send reprint requests to: Dr. Desmond J. Fitzgerald, Centre for Cardiovascular Science, Royal College of Surgeons in Ireland, St. Stephens Green, Dublin 2, Ireland.

  • ↵1 This work was supported by a grant from Helsinn Healthcare SA, Lugano, Switzerland and in part by the Health Research Board of Ireland. Previously presented at The Fourth International Congress on Essential Fatty Acids and Eicosanoids, July 20–24, 1997, Edinburgh, Scotland, poster presentation.

  • Abbreviations:
    Cox
    cyclooxygenase
    NSAIDs
    nonsteroidal anti-inflammatory drugs
    TMPP
    N N N′N′-tetramethyl-p-phenylenediamine dihydrochloride
    GC/MS
    gas chromatography, mass spectrometry
    EIA
    enzyme immunoassay
    PG
    prostaglandin
    TX
    thromboxane
    DMSO
    dimethyl sulfoxide
    • Received March 12, 1998.
    • Accepted June 30, 1998.
  • 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
Vol. 287, Issue 2
1 Nov 1998
  • Table of Contents
  • Index by author
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.
Selective Cyclooxygenase-2 Inhibition by Nimesulide in Man
(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 ArticleArticle

Selective Cyclooxygenase-2 Inhibition by Nimesulide in Man

Louise Cullen, Linda Kelly, Shane O. Connor and Desmond J. Fitzgerald
Journal of Pharmacology and Experimental Therapeutics November 1, 1998, 287 (2) 578-582;

Citation Manager Formats

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

Selective Cyclooxygenase-2 Inhibition by Nimesulide in Man

Louise Cullen, Linda Kelly, Shane O. Connor and Desmond J. Fitzgerald
Journal of Pharmacology and Experimental Therapeutics November 1, 1998, 287 (2) 578-582;
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
    • Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • CRV431 Decreases Liver Fibrosis and Tumor Development
  • Interaction of Diclofenac and Quinidine in Monkeys: Stimulation of Diclofenac Metabolism
  • Response-Rate Suppression in Operant Paradigm as Predictor of Soporific Potency in Rats and Identification of Three Novel Sedative-Hypnotic Neuroactive Steroids
Show more Article

Similar Articles

  • 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