Regulation of cyclooxygenase activity by metamizol

The ability of metamizol to inhibit cyclooxygenase-l and cyclooxygenase-2 a ctivities has been evaluated using different cyclooxygenase sources. Metami zol inhibited purified cyclooxygenase-l and cyclooxygenase-2 with an IC50 o f about 150 mu g/ml. A similar IC50 value for cyclooxygenase-2 was obtained in lipopolysaccharide-activated broken murine macrophages. Consistent with these findings, molecular models of the complexes between cyclooxygenase-l or cyclooxygenase-2 with 4-methylaminoantipyrine, the major active derivat ive of metamizol, suggested a common binding mode to both isoforms. In inta ct cells, however, the inhibition profiles were markedly different. The IC5 0 values of metamizol for cyclooxygenase-l in intact bovine aortic endothel ial cells (BAEC) cells and human platelets were 1730 +/- 150 mu g/ml and 48 6 +/- 56 mu g/ml, respectively. Inhibition of cyclooxygenase-2 activity in murine macrophages and primary human leukocytes activated by lipopolysaccha ride yielded IC50 values of 12 +/- 1.8 mu g/ml and 21 +/- 2.9 mu g/ml, resp ectively. These data indicate that the IC50 values obtained with purified e nzymes or disrupted cells cannot always be extrapolated to the cyclooxygena se inhibitory activity of nonsteroidal antiinflammatory drugs (NSAIDs) in i ntact cells. The data presented here also indicate that cyclooxygenase-2 in hibition could play an important role in the pharmacological effects of met amizol. (C) 1999 Elsevier Science B.V. All rights reserved.