A novel selective prostaglandin E2 synthesis inhibitor relieves pyrexia and arthritis in Guinea pigs inflammatory models

Journal of Pharmacological Sciences
Ryusuke SugitaKohei Shimada

Abstract

Prostaglandin E2 (PGE2), one of the terminal products in the cyclooxygenase pathway, plays an important role in various inflammatory responses. To determine whether selective inhibition of PGE2 may relieve these inflammatory symptoms, we synthesized a selective PGE2 synthesis inhibitor, compound A [1-(6-fluoro-5,7-dimethyl-1,3-benzothiazol-2-yl)-N-[(1S,2R)-2-(hydroxymethyl)cyclohexyl]piperidine-4-carboxamide], then investigated the effects on pyrexia, arthritis and inflammatory pain in guinea pigs. In LPS-stimulated guinea pig macrophages, compound A selectively inhibited inducible PGE2 biosynthesis in a dose-dependent manner whereas enhanced the formation of thromboxane B2 (TXB2). Compound A suppressed yeast-evoked PGE2 production selectively and enhanced the production of TXB2 and 6-keto PGF1αin vivo. In addition, compound A relieved yeast-induced pyrexia and also suppressed paw swelling in an adjuvant-induced arthritis model. The effect on gastrointestinal (GI) ulcer formation was also evaluated and compound A showed a lower GI adverse effect than indomethacin. However, compound A failed to relieve yeast-induced thermal hyperalgesia. These results suggest that selective inhibition of PGE2 synthesis may have anti-pyretic and ...Continue Reading

References

Jun 23, 1999·Proceedings of the National Academy of Sciences of the United States of America·P J JakobssonB Samuelsson
Dec 27, 2002·The New England Journal of Medicine·Francis K L ChanJoseph J Y Sung
Jul 2, 2003·Proceedings of the National Academy of Sciences of the United States of America·Catherine E TrebinoLaurent P Audoly
Oct 21, 2003·Nature Neuroscience·David EngblomAnders Blomqvist
May 14, 2004·The Journal of Biological Chemistry·Daisuke KameiIchiro Kudo
Jan 29, 2005·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Sipra SahaAnders Blomqvist
Feb 17, 2005·The New England Journal of Medicine·Nancy A NussmeierKenneth M Verburg
Feb 22, 2005·The Journal of Biological Chemistry·Catherine E TrebinoLaurent P Audoly
Sep 16, 2006·The Journal of Pharmacology and Experimental Therapeutics·Anne-Marie PulichinoLaurent P Audoly
Apr 19, 2008·Journal of Cellular and Molecular Medicine·Christian BrenneisGerd Geisslinger
Mar 27, 2013·Prostaglandins & Other Lipid Mediators·Patrick LeclercPer-Johan Jakobsson

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