The Effects of a Newly Developed Nonsteroidal Anti-inflammatory Drug (M-5011) on Arachidonic Acid Metabolism in Rheumatoid Synovail Fibroblasts

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Author(s)

Abstract

M-5011 (<I>d</I>-2-[4-(3-methyl-2-thienyl)phenyl]propionic acid) is a newly developed nonsteroidal anti-inflammatory drug (NSAID) that displays potent anti-inflammatory and analgesic properties with low ulcerogenic activities in animal models. In this study, the effects of M-5011 on arachidonic acid (AA) metabolism in synovial fibroblasts from patients with rheumatoid arthritis were evaluated and compared with those of other NSAIDs in vitro. Either M-5011 or ketoprofen potently inhibited prostaglandin (PG) E<SUB>2</SUB> production by cyclooxygenase (COX)-2 from exogenous AA in interleukin-1β (IL-1β)-stimulated cells. The IC<SUB>50</SUB> values of M-5011 and ketoprofen were 4.4 x 10<SUP>-7</SUP> and 5.9 × 10<SUP>-7</SUP> M, respectively. However, diclofenac and indomethacin were one order less potent. Although the latter two drugs exhibited timedependent and irreversible inhibition on COX-2 in IL-1β-stimulated cells, the inhibitory effects of M-5011 and ketoprofen were reversible. PGE<SUB>2</SUB> production by COX-1 from exogenous AA in non-stimulated cells was also inhibited by M-5011 with a potency less than that of ketoprofen. In addition, M-5011 inhibited [<SUP>14</SUP>C]AA release from prelabeled synovial cells stimulated with bradykinin. However, ketoprofen hardly affected the [<SUP>14</SUP>C]AA release. It is likely that the effects of M-5011 on AA metabolism are, in part, responsible for its in vivo efficacy and safety profile.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 75(4), 371-379, 1997-12-01

    The Japanese Pharmacological Society

References:  28

Cited by:  2

Codes

  • NII Article ID (NAID)
    10008190475
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    00215198
  • NDL Article ID
    4371103
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
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