Literature DB >> 18475454

The in vitro free radical scavenging activity of tenidap, a new dual cyclo-oxygenase and 5-1ipoxygenase inhibitor.

C S Lau1, J J Belch.   

Abstract

Tenidap, a new anti-inflammatory drug, is presently undergoing clinical studies as a treatment for rheumatoid arthritis (RA). Early pilot work has shown it to be of some benefit. Tenidap is a dual inhibitor of cyclo-oxygenase and 5-lipoxygenase enzymes. It has also been shown to modify white blood cell behaviour such as interleukin-1 production, monocyte differentiation and neutrophil degranulation. As free radicals (FRs) have been implicated in the pathogenesis of RA, we used an in vitro assay system developed by Misra and Fridovich to assess if tenidap has FR scavenging effects. Our study shows, for the first time, that tenidap has general FR scavenging effects although no effect on the superoxide anion (O2.-) could be demonstrated. This effect occurred in a dose-dependent manner at concentrations above 20 mug/ml (p < 0.005, Mann-Whitney U-test). As the therapeutic range of tenidap in serum is between 15 and 30 mug/ml such FR scavenging activity may be clinically relevant in the treatment of RA. Ex vivo confirmation of this possibility is underway.

Entities:  

Year:  1992        PMID: 18475454      PMCID: PMC2365331          DOI: 10.1155/S0962935192000231

Source DB:  PubMed          Journal:  Mediators Inflamm        ISSN: 0962-9351            Impact factor:   4.711


  11 in total

1.  Tenidap, in contrast to several available nonsteroidal antiinflammatory drugs, potently inhibits the release of activated neutrophil collagenase.

Authors:  W D Blackburn; L D Loose; L W Heck; W W Chatham
Journal:  Arthritis Rheum       Date:  1991-02

2.  An approach to free radicals.

Authors:  T L Dormandy
Journal:  Lancet       Date:  1983-10-29       Impact factor: 79.321

Review 3.  Eicosanoids in inflammation.

Authors:  G A Higgs; S Moncada; J R Vane
Journal:  Ann Clin Res       Date:  1984

4.  Evaluation of Tenidap (CP-66,248) on human neutrophil arachidonic acid metabolism, chemotactic potential and clinical efficacy in the treatment of rheumatoid arthritis.

Authors:  D M Smith; J A Johnson; R Loeser; R A Turner
Journal:  Agents Actions       Date:  1990-08

Review 5.  Eicosanoids and rheumatology: inflammatory and vascular aspects.

Authors:  J J Belch
Journal:  Prostaglandins Leukot Essent Fatty Acids       Date:  1989-06       Impact factor: 4.006

6.  Lipid peroxidation in rheumatoid arthritis: thiobarbituric acid-reactive material and catalytic iron salts in synovial fluid from rheumatoid patients.

Authors:  D Rowley; J M Gutteridge; D Blake; M Farr; B Halliwell
Journal:  Clin Sci (Lond)       Date:  1984-06       Impact factor: 6.124

7.  Gliclazide: a general free radical scavenger.

Authors:  N A Scott; P E Jennings; J Brown; J J Belch
Journal:  Eur J Pharmacol       Date:  1991-10-14       Impact factor: 4.432

8.  A comparison of the free radical scavenging activity of leukotrienes and prostaglandins.

Authors:  M Chopra; J J Belch; W E Smith
Journal:  Free Radic Res Commun       Date:  1988

9.  CP-66,248, a new anti-inflammatory agent, is a potent inhibitor of leukotriene B4 and prostanoid synthesis in human polymorphonuclear leucocytes in vitro.

Authors:  E Moilanen; J Alanko; M Z Asmawi; H Vapaatalo
Journal:  Eicosanoids       Date:  1988

10.  Captopril: a free radical scavenger.

Authors:  M Chopra; N Scott; J McMurray; J McLay; A Bridges; W E Smith; J J Belch
Journal:  Br J Clin Pharmacol       Date:  1989-03       Impact factor: 4.335

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