Cookies Policy
X

This site uses cookies. By continuing to browse the site you are agreeing to our use of cookies.

I accept this policy

Find out more here

The pharmacological profile of ML3000: A new pyrrolizine derivative inhibiting the enzymes cyclo-oxygenase and 5-lipoxygenase

No metrics data to plot.
The attempt to load metrics for this article has failed.
The attempt to plot a graph for these metrics has failed.
The full text of this article is not currently available.

Brill’s MyBook program is exclusively available on BrillOnline Books and Journals. Students and scholars affiliated with an institution that has purchased a Brill E-Book on the BrillOnline platform automatically have access to the MyBook option for the title(s) acquired by the Library. Brill MyBook is a print-on-demand paperback copy which is sold at a favorably uniform low price.

Access this article

+ Tax (if applicable)
Add to Favorites
You must be logged in to use this functionality

image of Inflammopharmacology

Since the discovery of aspirin about one century ago, many non-steroidal anti-inflammatory drugs (NSAIDs) have been used for the treatment of inflammatory states and pain. While the NSAIDs are generally safe and effective, common side effects frequently limit therapy. Typical mechanism-based side effects are gastrointestinal (GI)-related, ranging from GI upset and intolerance to ulceration and bleeding after long-term therapy. In order to overcome these side effects several strategies have been followed, among them the development of selective COX-2 inhibitors. Our strategy to find compounds that are active on the one hand and tolerated by the GI tract on the other hand, is based on the shunt to leukotrienes. This theory is founded upon the fact that NSAIDs, while inhibiting the cyclooxygenase branch of the arachidonic acid cascade, are able to increase the 5-lipoxygenase (5-LOX) branch of arachidonic acid metabolism. This shunt to the 5-LOX side leads to the increase in chemotactic LTB4 and vasoconstrictive peptidoleukotrienes, the contributory effects of which to gastrointestinal disorders are widely accepted. Therefore, the design of anti-inflammatory compounds with 5-LOX inhibitory effects seems reasonable. With the compound ML3000, this theory has gained further evidence. ML3000 is an anti-inflammatory compound with potent activity in various animal experiments that represent models for acute and chronic inflammation, pain, fever and asthma. It is a balanced inhibitor of the enzymes 5-LOX and COX-1/2 in the submicromolar range. The compound demonstrates excellent gastrointestinal tolerance in various animal species. The preclinical profile of ML3000, which is currently in Phase III clinical development, is presented in this publication.

Affiliations: 1: R&D Division, Merckle GmbH, Dr.-Georg-Spohn-Str 7, 89143 Blaubeuren, Germany; 2: Institute of Pharmacy, University of Tuebingen, D-72076 Tuebingen, Germany

10.1163/156856001300248380
/content/journals/10.1163/156856001300248380
dcterms_title,pub_keyword,dcterms_description,pub_author
6
3
Loading
Loading

Full text loading...

/content/journals/10.1163/156856001300248380
Loading

Data & Media loading...

http://brill.metastore.ingenta.com/content/journals/10.1163/156856001300248380
Loading

Article metrics loading...

/content/journals/10.1163/156856001300248380
2001-05-31
2016-12-02

Sign-in

Can't access your account?
  • Tools

  • Add to Favorites
  • Printable version
  • Email this page
  • Subscribe to ToC alert
  • Get permissions
  • Recommend to your library

    You must fill out fields marked with: *

    Librarian details
    Your details
    Why are you recommending this title?
    Select reason:
     
    Inflammopharmacology — Recommend this title to your library
  • Export citations
  • Key

  • Full access
  • Open Access
  • Partial/No accessInformation