Regulation of cyclooxygenase activity by metamizol
AuthorsCampos, Carmen; Gregorio, Rosa de; García Nieto, Raquel; Gago Badenas, Federico; Ortiz Betés, Pablo; [et al.]
IdentifiersPermanent link (URI): http://hdl.handle.net/10017/5074
European Journal of Pharmacology 378 (1999) 339-347
The ability of metamizol to inhibit cyclooxygenase-l and cyclooxygenase-2 activities has been evaluated using different cyclooxygenase sources. Metamizol inhibited purified cyclooxygenase-l and cyclooxygenase-2 with an IC50 of 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 derivative of metamizol, suggested a common binding mode to both isoforms. In intact cells, however, the inhibition profiles were markedly different. The IC50 values of metamizol for cyclooxygenase-l in intact bovine aortic endothelial cells (BAEC) cells and human platelets were 1730 +/- 150 mu g/ml and 486 +/- 56 mu g/ml, respectively. Inhibition of cyclooxygenase-2 activity in murine macrophages and primary human leukocytes activated by lipopolysaccharide yielded IC50 values of 12 +/- 1.8 mu g/ml and 21 +/- 2.9 mu g/ml, respectively. These data indicate that the IC50 values obtained with purified enzymes or disrupted cells cannot always be extrapolated to 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. (C) 1999 Elsevier Science B.V. All rights reserved.
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