imrecoxib and Edema

We have developed a novel and moderately selective COX-2 inhibitor, imrecoxib, as a new anti-inflammatory drug. We describe herein the preparation of the major metabolites M2 and M4 of imrecoxib, as well as the in vitro and in vivo activities of the two compounds. The results showed that both M2 and M4 are potential COXs inhibitors with a moderate COX-1/COX-2 selectivity, and their anti-inflammatory activity in vivo was equal to or slightly higher than the clinical celecoxib.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Celecoxib; Cyclooxygenase 2 Inhibitors; Dose-Response Relationship, Drug; Edema; Humans; Mice; Pyrazoles; Pyrroles; Rats; Sulfides; Sulfonamides

To investigate the inhibitory effect of imrecoxib, a synthetic compound of completely new structure, on cyclooxygenase 1 (COX-1) and 2 (COX-2) and its anti-inflammatory effect in vivo.. The inhibitory effects of imrecoxib on cyclooxygenase 1 and 2 were studied using whole cell assay with murine peritoneal macrophages induced by calcimycin and LPS. The inhibitory effects of imrecoxib on mRNA level of COX-1 and COX-2 in human macrophage cell line U937 were detected by reverse transcription polymerase chain reaction (RT-PCR) analysis. Effects of imrecoxib on acute and chronic inflammation were evaluated in rat carrageenan induced edema model and rat adjuvant-induced arthritis model, respectively.. Imrecoxib was found to inhibit COX-1 and COX-2 with IC50 value of 115+/-28 nmol/L and 18+/-4 nmol/L, respectively. Imrecoxib was shown to selectively and dose-dependently inhibit COX-2 mRNA level. Imrecoxib effectively inhibited carrageenan-induced acute inflammation at the doses of 5, 10, and 20 mg/kg i.g. and adjuvant-induced chronic inflammation at the doses of 10 and 20 mg/kg/d i.g.. Imrecoxib is a novel and moderately selective COX-2 inhibitor that possesses anti-inflammatory effect by inhibition of COX-2 mRNA expression.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Edema; Humans; Isoenzymes; Male; Membrane Proteins; Mice; Mice, Inbred C57BL; Prostaglandin-Endoperoxide Synthases; Pyrroles; Rats; Rats, Wistar; RNA, Messenger; Sulfides; U937 Cells