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 ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

SSR240612 [(2R)-2-[((3R)-3-(1,3-Benzodioxol-5-yl)-3-{[(6-methoxy-2-naphthyl)sulfonyl]amino}propanoyl)amino]-3-(4-{[2R,6S)-2,6-dimethylpiperidinyl]methyl}phenyl)-N-isopropyl-N-methylpropanamide Hydrochloride], a New Nonpeptide Antagonist of the Bradykinin B1 Receptor: Biochemical and Pharmacological Characterization

Jean Gougat, Bernard Ferrari, Lionel Sarran, Claudine Planchenault, Martine Poncelet, Jeanne Maruani, Richard Alonso, Annie Cudennec, Tiziano Croci, Fabio Guagnini, Katalin Urban-Szabo, Jean-Pierre Martinolle, Philippe Soubrié, Olivier Finance and Gérard Le Fur
Journal of Pharmacology and Experimental Therapeutics May 2004, 309 (2) 661-669; DOI: https://doi.org/10.1124/jpet.103.059527
Jean Gougat
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bernard Ferrari
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lionel Sarran
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Claudine Planchenault
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Martine Poncelet
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jeanne Maruani
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Richard Alonso
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Annie Cudennec
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tiziano Croci
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Fabio Guagnini
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Katalin Urban-Szabo
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jean-Pierre Martinolle
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Philippe Soubrié
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Olivier Finance
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gérard Le Fur
  • 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

The biochemical and pharmacological properties of a novel non-peptide antagonist of the bradykinin (BK) B1 receptor, SSR240612 [(2R)-2-[((3R)-3-(1,3-benzodioxol-5-yl)-3-{[(6-methoxy-2-naphthyl)sulfonyl]amino}propanoyl)amino]-3-(4-{[2R,6S)-2,6-dimethylpiperidinyl]methyl}phenyl)-N-isopropyl-N-methylpropanamide hydrochloride] were evaluated. SSR240612 inhibited the binding of [3H]Lys0-des-Arg9-BK to the B1 receptor in human fibroblast MRC5 and to recombinant human B1 receptor expressed in human embryonic kidney cells with inhibition constants (Ki) of 0.48 and 0.73 nM, respectively. The compound selectivity for B1 versus B2 receptors was in the range of 500- to 1000-fold. SSR240612 inhibited Lys0-desAr9-BK (10 nM)-induced inositol monophosphate formation in human fibroblast MRC5, with an IC50 of 1.9 nM. It also antagonized des-Arg9-BK-induced contractions of isolated rabbit aorta and mesenteric plexus of rat ileum with a pA2 of 8.9 and 9.4, respectively. Antagonistic properties of SSR240612 were also demonstrated in vivo. SSR240612 inhibited des-Arg9-BK-induced paw edema in mice (3 and 10 mg/kg p.o. and 0.3 and 1 mg/kg i.p.). Moreover, SSR240612 reduced capsaicin-induced ear edema in mice (0.3, 3 and 30 mg/kg p.o.) and tissue destruction and neutrophil accumulation in the rat intestine following splanchnic artery occlusion/reperfusion (0.3 mg/kg i.v.). The compound also inhibited thermal hyperalgesia induced by UV irradiation (1 and 3 mg/kg p.o.) and the late phase of nociceptive response to formalin in rats (10 and 30 mg/kg p.o.). Finally, SSR240612 (20 and 30 mg/kg p.o.) prevented neuropathic thermal pain induced by sciatic nerve constriction in the rat. In conclusion, SSR240612 is a new, potent, and orally active specific non-peptide bradykinin B1 receptor antagonist.

Footnotes

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

  • DOI: 10.1124/jpet.103.059527.

  • ABBREVIATIONS. BK, bradykinin; SSR240612, (2R)-2-[((3R)-3-(1,3-benzodioxol-5-yl)-3-{[(6-methoxy-2-naphthyl)sulfonyl]amino}propanoyl)amino]-3-(4-{[2R,6S)-2,6-dimethylpiperidinyl]methyl}phenyl)-N-isopropyl-N-methylpropanamide hydrochloride; HEK, human embryonic kidney; DMEM, Dulbecco's modified Eagle's medium; IL-1β, interleukin-1β; TES, 2-{[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]amino}ethanesulfonic acid; BSA, bovine serum albumin; CHO, Chinese hamster ovary; ANOVA, analysis of variance; MPO, myeloperoxidase.

    • Received September 4, 2003.
    • Accepted January 21, 2004.
  • 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: 309 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 309, Issue 2
1 May 2004
  • Table of Contents
  • About the Cover
  • 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.
SSR240612 [(2R)-2-[((3R)-3-(1,3-Benzodioxol-5-yl)-3-{[(6-methoxy-2-naphthyl)sulfonyl]amino}propanoyl)amino]-3-(4-{[2R,6S)-2,6-dimethylpiperidinyl]methyl}phenyl)-N-isopropyl-N-methylpropanamide Hydrochloride], a New Nonpeptide Antagonist of the Bradykinin…
(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 ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

SSR240612 [(2R)-2-[((3R)-3-(1,3-Benzodioxol-5-yl)-3-{[(6-methoxy-2-naphthyl)sulfonyl]amino}propanoyl)amino]-3-(4-{[2R,6S)-2,6-dimethylpiperidinyl]methyl}phenyl)-N-isopropyl-N-methylpropanamide Hydrochloride], a New Nonpeptide Antagonist of the Bradykinin B1 Receptor: Biochemical and Pharmacological Characterization

Jean Gougat, Bernard Ferrari, Lionel Sarran, Claudine Planchenault, Martine Poncelet, Jeanne Maruani, Richard Alonso, Annie Cudennec, Tiziano Croci, Fabio Guagnini, Katalin Urban-Szabo, Jean-Pierre Martinolle, Philippe Soubrié, Olivier Finance and Gérard Le Fur
Journal of Pharmacology and Experimental Therapeutics May 1, 2004, 309 (2) 661-669; DOI: https://doi.org/10.1124/jpet.103.059527

Citation Manager Formats

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

SSR240612 [(2R)-2-[((3R)-3-(1,3-Benzodioxol-5-yl)-3-{[(6-methoxy-2-naphthyl)sulfonyl]amino}propanoyl)amino]-3-(4-{[2R,6S)-2,6-dimethylpiperidinyl]methyl}phenyl)-N-isopropyl-N-methylpropanamide Hydrochloride], a New Nonpeptide Antagonist of the Bradykinin B1 Receptor: Biochemical and Pharmacological Characterization

Jean Gougat, Bernard Ferrari, Lionel Sarran, Claudine Planchenault, Martine Poncelet, Jeanne Maruani, Richard Alonso, Annie Cudennec, Tiziano Croci, Fabio Guagnini, Katalin Urban-Szabo, Jean-Pierre Martinolle, Philippe Soubrié, Olivier Finance and Gérard Le Fur
Journal of Pharmacology and Experimental Therapeutics May 1, 2004, 309 (2) 661-669; DOI: https://doi.org/10.1124/jpet.103.059527
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
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Lipopolysaccharide Induces Epithelium- and Prostaglandin E2-Dependent Relaxation of Mouse Isolated Trachea through Activation of Cyclooxygenase (COX)-1 and COX-2
  • Cannabinoid-Mediated Elevation of Intracellular Calcium: A Structure-Activity Relationship
  • Protease-Activated Receptor-2 Peptides Activate Neurokinin-1 Receptors in the Mouse Isolated Trachea
Show more INFLAMMATION AND IMMUNOPHARMACOLOGY

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