Regulation of cyclooxygenase activity by metamizol

The ability of metamizol to inhibit cyclooxygenase-1 and cyclooxygenase-2 activities has been evaluated using different cyclooxy-genase sources. Metamizol inhibited purified cyclooxygenase-1 and cyclooxygenase-2 with an IC of about 150 mgrml. A similar IC50 50 value for cyclooxygenase-2 was obtained in lipopolysaccharide-activated broken murine macrophages. Consistent with these findings, molecular models of the complexes between cyclooxygenase-1 or cyclooxygenase-2 with 4-methylaminoantipyrine, the major active derivative of metamizol, suggested a common binding mode to both isoforms. In intact cells, however, the inhibition profiles were .markedly different. The IC values of metamizol for cyclooxygenase-1 in intact bovine aortic endothelial cells BAEC cells and human50 platelets were 1730"150 mgrml and 486"56 mgrml, respectively. Inhibition of cyclooxygenase-2 activity in murine macrophages and primary human leukocytes activated by lipopolysaccharide yielded IC values of 12"1.8 mgrml and 21"2.9 mgrml,50 respectively. These data indicate that the IC values obtained with purified enzymes or disrupted cells cannot always be extrapolated to50 .the cyclooxygenase inhibitory activity of nonsteroidal antiinflammatory drugs NSAIDs in intact cells. The data presented here also indicate that cyclooxygenase-2 inhibition could play an important role in the pharmacological effects of metamizol. q 1999 Elsevie