Abstract | AIM: 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. METHODS: 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. RESULTS:
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. CONCLUSION:
Imrecoxib is a novel and moderately selective COX-2 inhibitor that possesses anti-inflammatory effect by inhibition of COX-2 mRNA expression.
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Authors | Xiao-hong Chen, Jin-ye Bai, Fang Shen, Ai-ping Bai, Zong-ru Guo, Gui-fang Cheng |
Journal | Acta pharmacologica Sinica
(Acta Pharmacol Sin)
Vol. 25
Issue 7
Pg. 927-31
(Jul 2004)
ISSN: 1671-4083 [Print] United States |
PMID | 15210067
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Inflammatory Agents, Non-Steroidal
- Cyclooxygenase 2 Inhibitors
- Cyclooxygenase Inhibitors
- Imrecoxib
- Isoenzymes
- Membrane Proteins
- Pyrroles
- RNA, Messenger
- Sulfides
- Cyclooxygenase 1
- Cyclooxygenase 2
- PTGS1 protein, human
- PTGS2 protein, human
- Prostaglandin-Endoperoxide Synthases
- Ptgs1 protein, mouse
- Ptgs1 protein, rat
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Topics |
- Animals
- Anti-Inflammatory Agents, Non-Steroidal
(pharmacology)
- Arthritis, Experimental
(pathology)
- Cyclooxygenase 1
- Cyclooxygenase 2
- Cyclooxygenase 2 Inhibitors
- Cyclooxygenase Inhibitors
(pharmacology)
- Edema
(pathology)
- Humans
- Isoenzymes
(antagonists & inhibitors, biosynthesis, genetics)
- Male
- Membrane Proteins
- Mice
- Mice, Inbred C57BL
- Prostaglandin-Endoperoxide Synthases
(biosynthesis, genetics)
- Pyrroles
(chemical synthesis, pharmacology)
- RNA, Messenger
(genetics)
- Rats
- Rats, Wistar
- Sulfides
(chemical synthesis, pharmacology)
- U937 Cells
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