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

• Tobetto Kenji

  Research & Development Laboratories, Maruho Co., Ltd.

• Yamamoto Yumiko

  Research & Development Laboratories, Maruho Co., Ltd.

• Kataoka Masanori

  Research & Development Laboratories, Maruho Co., Ltd.

• Ando Takao

  Research & Development Laboratories, Maruho Co., Ltd.

• Sugimoto Kenji

  Department of Applied Biochemistry, Faculty of Agriculture, University of Osaka Prefecture

• Himeno Michio

  Department of Applied Biochemistry, Faculty of Agriculture, University of Osaka Prefecture

Bibliographic Information

Other Title

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

Abstract

M-5011 (d-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) E₂ production by cyclooxygenase (COX)-2 from exogenous AA in interleukin-1β (IL-1β)-stimulated cells. The IC₅₀ values of M-5011 and ketoprofen were 4.4 x 10^-7 and 5.9 × 10^-7 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. PGE₂ 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 [¹⁴C]AA release from prelabeled synovial cells stimulated with bradykinin. However, ketoprofen hardly affected the [¹⁴C]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

  The Japanese Pharmacological Society

Keywords

• M-5011
• NSAID
• Synovial cell
• Cyclooxygenase
• Arachidonic acid metabolism

Details

• CRID: 1390282679261222144
• NII Article ID: 10008190475
• NII Book ID: AA00691188
• DOI: 10.1254/jjp.75.371
• COI: 1:CAS:528:DyaK1cXhtVOq
• ISSN: 13473506
• ISSN: 00215198
• NDL BIB ID: 4371103
• PubMed: 9469643
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I4371103
• Web Site: https://api.elsevier.com/content/article/PII:S0021519819312880?httpAccept=text/xml
• Web Site: https://api.elsevier.com/content/article/PII:S0021519819312880?httpAccept=text/plain
• Web Site: https://search.jamas.or.jp/link/ui/1998086199
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
• Abstract License Flag: Disallowed