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, Volume 20, Issue 1–2, pp 113–123 | Cite as

Pharmacologic characterization of the antiinflammatory properties of a new dual inhibitor of lipoxygenase and cyclooxygenase

  • M. J. DiMartino
  • D. E. Griswold
  • B. A. Berkowitz
  • G. Poste
  • N. Hanna
Immunosuppression and Inflammation

Abstract

SK&F 86002 [6-(4-fluorophenyl)2,3-dihydro-5-(4-pyridinyl)imidazo(2,1-b)thiazole], a dual inhibitor of arachidonic acid metabolism, administered orally to rats prevented the development of carrageenan-induced edema, immune- and nonimmune-mediated inflammation of adjuvant-induced arthritis (AA) and reduced established inflammation in AA and collagen type II-induced arthritis. A similar profile of activity was observed following treatment with the cyclooxygenase inhibitor, indomethacin. However, unlike other nonsteroidal antiinflammatory drugs, SK&F 86002 exhibited antiinflammatory activity in inflammation models that are insensitive to cyclooxygenase inhibitors such as the established inflammation in carrageenan-induced edema and the edema induced by arachidonic acid and platelet activating factor. Moreover, SK&F 86002, but not indomethacin, inhibited the immune-mediated inflammatory responses evoked in sensitized animals by challenge with purified protein derivative. In addition, SK&F 86002 produced dose-related analgesia in mice, which was not reversed by the narcotic antagonist, naltexone. SK&F 86002 thus represents an orally active antiarthritic and analgesic compound with novel antiinflammatory properties.

Keywords

Arachidonic Acid Indomethacin Thiazole Platelet Activate Factor Antiinflammatory Property 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

NSAIDS

Nonsteroidal Antiinflammatory Drugs

PPQ

Phenyl-p-benzoquinone

AA

Adjuvant arthritis

PPD

Purified protein derivative

SRBC

Sheep red blood cells

IP

Intraperitoneal

PO

Per os

SC

Subcutaneous

DTH

Delayed type hypersensitivity

FCA

Freund's complete adjuvant

PMN

Polymorphonuclear

PAF

Platelet activating factor

ADX

Adrenalectomized

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Copyright information

© Birkhäuser Verlag 1987

Authors and Affiliations

  • M. J. DiMartino
    • 1
  • D. E. Griswold
    • 1
  • B. A. Berkowitz
    • 1
  • G. Poste
    • 1
  • N. Hanna
    • 1
  1. 1.Research and Development DivisionSmith Kline & French LaboratoriesSwedeland

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