A Novel Selective Prostaglandin E sub(2) Synthesis Inhibitor Relieves Pyrexia and Chronic Inflammation in Rats

• Published in: Inflammation 2016-04, Vol.39 (2), p.907-915
• Main Authors: Sugita, Ryusuke, Kuwabara, Harumi, Sugimoto, Kotaro, Kubota, Kazufumi, Imamura, Yuichiro, Kiho, Toshihiro, Tengeiji, Atsushi, Kawakami, Katsuhiro, Shimada, Kohei
• Format: Article
• Language: English
• ISSN: 0360-3997; 1573-2576
• DOI: 10.1007/s10753-016-0323-5

Prostaglandin E sub(2) (PGE sub(2)) is a terminal prostaglandin in the cyclooxygenase (COX) pathway. Inhibition of PGE sub(2) production may relieve inflammatory symptoms such as fever, arthritis, and inflammatory pain. We report here the profile of a novel selective PGE sub(2) synthesis inhibitor, compound A [N-[(1S,3S)-3-ca rbamoylcyclohexyl]-1-(6-methyl-3-phenylquinolin-2-yl)piperidine-4- c a rboxamide], in animal models of pyrexia and inflammation. The compound selectively suppressed the synthesis of PGE sub(2) in human alveolar adenocarcinoma cell line A549 cells and rat macrophages. In the lipopolysaccharide-induced pyrexia model, this compound selectively reduced PGE sub(2) production in cerebrospinal fluid and showed an anti-pyretic effect. In the adjuvant-induced arthritis model, compound A therapeutically decreased foot swelling in the established arthritis. Our data demonstrates that selective suppression of PGE sub(2) synthesis shows anti-pyretic and anti-inflammatory effects, suggesting that selective PGE sub(2) synthesis inhibitors can be applied as an alternative treatment to nonsteroidal, anti-inflammatory drugs (NSAIDs) or COX-2-selective inhibitors.