The Anti-inflammatory Effect of FR188582, a Highly Selective Inhibitor of Cyclooxygenase-2, With an Ulcerogenic Sparing Effect in Rats
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概要
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The anti-inflammatory and ulcerogenic effects of FR188582, 3-chloro-5-[4-(methylsulfonyl) phenyl]-1-phenyl-1H-pyrazole, were investigated. In a recombinant human cyclooxygenase (COX) enzyme activity, FR188582 inhibited COX-2 with an IC50 value of 0.017 μM, and the inhibition of prostaglandin (PG) E2 formation by FR188582 was over 6000 times more selective for COX-2 than COX-1. Oral administration of FR188582 dose-dependently inhibited adjuvant arthritis. This effect was threefold more potent than that of indomethacin. FR188582 and indomethacin dose-dependently suppressed the formation of immunoreactive PGE2, but not immunoreactive leukotriene (LT) B4, in arthritic paw. Unlike indomethacin, FR188582 did not induce visible gastric lesions in rats at doses up to 32 mg/kg, p.o. Furthermore, FR188582 did not inhibit the level of immunoreactive PGE2 and immunoreactive 6-keto PGF1α in rat gastric mucosa. These results suggest that FR188582, a highly selective COX-2 inhibitor, has a potent anti-inflammatory effect mediated by inhibition of PGE2 in inflamed tissues. The safety profile of FR188582 appears to be improved over the safety profile of indomethacin.
- 社団法人 日本薬理学会の論文
- 2001-02-01
著者
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Yamase-sugiyama Aiko
Research Information Management Division Fujisawa Pharmaceutical Co. Ltd.
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SAKANE Kazuo
Medicinal Chemistry Research Laboratories, Fujisawa Pharmaceutical Co., Ltd.
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TANAKA Hirokazu
Research Institute of Applied Electricity,Hokkaido University
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Sakane Kazuo
Medicinal Chemistry Research Laboratories
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Sakane Kazuo
Medicinal Chemistry Research Labortories Fujisawa Pharmaceutical Co. Ltd.
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Ochi T
Department Of Immunology And Inflammation Medicinal Biology Research Laboratories Fujisawa Pharmaceu
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Ochi Takehiro
Department Of Immunology And Inflammation Medicinal Biology Research Laboratories Fujisawa Pharmaceu
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Ochi Takehiro
Department Of Electronic Chemistry Tokyo Institute Of Technology
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OHKUBO Yoshitaka
Department of Immunology and Inflammation, Medicinal Biology Research Laboratories, Fujisawa Pharmac
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Ohkubo Yoshitaka
Department Of Immunology And Inflammation Medicinal Biology Research Laboratories Fujisawa Pharmaceu
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Tanaka Hirokazu
Research Institute Of Applied Electricity Hokkaido University
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Tanaka Hirokazu
Research Information Management Division Fujisawa Pharmaceutical Co. Ltd.
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Yamane-Sugiyama Aiko
Research Information Management Division, Fujisawa Pharmaceutical Co., Ltd.
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