ISSN:
1420-908X
Keywords:
Cox-2 inhibitors
;
CGP-28238
;
NS-398
;
SC-58125
;
L-745,337
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract In this study, PGE2 levels in lipopolysaccharide (LPS)-challenged human whole blood and TxB2 levels following blood coagulation were measured as biochemical index for cyclooxygenase (Cox)-2 and Cox-1 activity respectively. Incubation of human mononuclear cells isolated from whole blood with LPS (100 μ//mL) induced a time-dependent increase in the expression of Cox-2 protein (〉100 fold at 24hr). This is associated with increases in PGE2 production and free arachidonate release in the plasma. Cox-1 protein was detected in the human mononuclear cells at time zero but was not induced by either LPS or PBS. Most non-steroidal antiinflammatory drugs (NSAIDs) are more potent at inhibiting Cox-1 than Cox-2. Five experimental compounds CGP-28238, Dup-697, NS-398, SC-58125 and L-745,337, have a greater selectivity for Cox-2. Indomethacin at a single oral dose (25 mg) inhibited approximately 90% the whole blood Cox-2 and Cox-1 activities ex vivo in healthy subjects. These results support the use of this assay to assess the biochemical efficacy of selective Cox-2 inhibitors in clinical trials.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF02265118
Permalink