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

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-carbamoylcyclohexyl]-1-(6-methyl-3-phenylquinolin-2-yl)piperidine-4-carboxamide], 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.