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

  • Immunosuppression and Inflammation
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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.

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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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Authors and Affiliations

  1. Research and Development Division, Smith Kline & French Laboratories, 709 Swedeland Road (L-101), 19479, Swedeland, PA

    M. J. DiMartino, D. E. Griswold, B. A. Berkowitz, G. Poste & N. Hanna

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  1. M. J. DiMartino
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  2. D. E. Griswold
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  3. B. A. Berkowitz
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  4. G. Poste
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  5. N. Hanna
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DiMartino, M.J., Griswold, D.E., Berkowitz, B.A. et al. Pharmacologic characterization of the antiinflammatory properties of a new dual inhibitor of lipoxygenase and cyclooxygenase. Agents and Actions 20, 113–123 (1987). https://doi.org/10.1007/BF01965633

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  • DOI: https://doi.org/10.1007/BF01965633

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