The Profile of FR140423, a Novel Anti-inflammatory Compound, in Yeast-Induced Rat Hyperalgesia

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Author(s)

    • Ochi Takehiro OCHI Takehiro
    • Department of Immunology and Inflammation, Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd.
    • Fujii Takashi FUJII Takashi
    • Department of Immunology and Inflammation, Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd.
    • GOTO Toshio
    • Department of Immunology and Inflammation, Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd.

Abstract

The mechanism of action of FR140423 (3-(difluoromethyl)-1-(4-methoxyphenyl)-5-[4-(methylsulfinyl)phenyl]pyrazole), a novel anti-inflammatory compound, in a rat yeast-induced hyperalgesic model was investigated and compared with those of indomethacin and morphine. We tested the inhibitory effects of FR140423 on the formation of arachidonic acid metabolites, prostaglandin (PG) E<SUB>2</SUB>, thromboxane (TX) B<SUB>2</SUB> and leukotriene (LT) B<SUB>4</SUB>, in yeast-injected inflamed paws and the effect of the opioid receptor antagonist naloxone on FR140423-induced anti-hyperalgesic effect and inhibition of the formation of arachidonic acid metabolites. Oral administration of FR140423 showed a dose-dependent anti-hyperalgesic effect. This effect was fourfold more potent than that of indomethacin but less potent than that of morphine. Unlike morphine, FR140423 suppressed the levels of PGE<SUB>2</SUB> and TXB<SUB>2</SUB> but not LTB<SUB>4</SUB> in inflamed paws. FR140423 did not inhibit yeast-induced paw edema. The anti-hyperalgesic effect of FR140423 in yeast-injected rat paws was partially blocked by naloxone. However, the inhibitory effects of FR140423 on the formation of PGE<SUB>2</SUB> and TXB<SUB>2</SUB> in yeast-injected rat paws were not antagonized by naloxone. These results suggest that FR140423 shows a potent anti-hyperalgesic effect mediated by inhibition of PGs in inflamed tissue and by activation of opioid receptors.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 81(1), 94-98, 1999-09

    The Japanese Pharmacological Society

References:  18

Codes

  • NII Article ID (NAID)
    10008196305
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    00215198
  • NDL Article ID
    4867912
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  NDL  J-STAGE 
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