Cyclooxygenase 1 COX

Coronary circulation, 6 (1969) 11 Corticotropin releasing factor receptor antagonists, 41 (2003) 195 Coumarins, metabolism and biological actions, 10 (1974) 85 Cyclic AMP, 12 (1975) 293 Cyclooxygenase-2 (COX-2) inhibitors, 36 (1999) 201... 

Cyclooxygenase-2 (COX-2) Inhibitors and Non-steroidal Anti-Inflammatory Drugs (NSAIDs)... 

Selective cyclooxygenase-2 (COX-2) inhibitors have not been shown to be any more effective than the combination of a PPI... 

Clinical trial evidence supports many NSAID medications in the acute treatment of migraines with and without aura.30 The currently marketed cyclooxygenase-2 (COX-2) selective... 

NSAIDs are associated with gastrointestinal, renal, hepatic, and central nervous system toxicity and may increase blood pressure. NSAIDs that are selective for the cyclooxygenase-2 (COX-2) isozyme are less likely to cause gastrointestinal complications but may increase the risk of cardiovascular events. They are no more effective than nonselective NSAIDs. Selective agents should be reserved for patients at high risk of gastrointestinal complications and low risk for cardiovascular events. 

Cyclooxygenase-2 (COX-2)-selective inhibitors produce results comparable with those of traditional NSAIDs. However, cardiovascular safety concerns and the high cost of COX-2 inhibitors argue against their use for this disorder. 

Additional genes and protein receptors are believed to be important in colorectal tumorigenesis. Cyclooxygenase 2 (COX-2), which is induced in colorectal cancer cells, influences apoptosis and other cellular functions in colon cells, and overexpression of the epidermal growth factor receptor (EGFR), a transmembrane glycoprotein involved... 

The efficacy and safety of cyclooxygenase-2 (COX-2) selective inhibitors (e.g., celecoxib) have not been fully assessed in gouty arthritis, but they are more costly than conventional NSAIDs and are unlikely to result in fewer GI complications because of the short duration of therapy. 

Compound 330 (Figure 31) is a potent and very selective cyclooxygenase-2 (COX-2) inhibitor <1997BMCL57>. Three-dimensional quantity-structure activity relationship (3-D QSAR) analysis of this compound and other members of a series of 5,6-diarylthiazolo[3,2-A][l,2,4]triazoles has been carried out <2004MI5>. 

While comparatively few dihydrodiols have been observed in the metabolism of phenyl-containing drugs, the examples above are far from unique. Thus, oxazepam incubated in rat, mouse, and human microsomes did yield a dihydrodiol besides the para-phenol [82], A more-recent example is that of rofecoxib (10.22), a potent and selective cyclooxygenase-2 (COX-2) inhibitor. In rats and dogs, phenyl oxidation produced 4 -hydroxyrofecoxib and rof-ecoxib-3, 4 -dihydrodiol as urinary metabolites of intermediate quantitative importance [83]. 

The cells in the hypothalamus that control body temperature respond to the cytokines by stimulating the activity of the membrane bound phospholipase, which results in the formation of arachidonic acid, the substrate for the enzyme cyclooxygenase-2 (COX-2) which is the rate-limiting step in the pathway for synthesis of prostaglandins. Prostaglandins influence cells in the hypothalamus that are responsible for temperature regulation. 

Steinauer KK, Gibbs I, Ning S, et al. Radiation induces upregulation of cyclooxygenase-2 (COX-2) protein in PC-3 cells. IntJRadiat Oncol Biol Phys 2000 48 325-328. 

Hosomi Y, Yokose T, Hirose Y, et al. Increased cyclooxygenase 2 (COX-2) expression occurs frequently in precursor lesions of human adenocarcinoma of the lung. Lung Cancer 2000 30 73-81. 

Mohammed SI, Knapp DW, Bostwick DG, et al. Expression of cyclooxygenase-2 (COX-2) in human invasive transitional cell carcinoma (TCC) of the urinary bladder. Cancer Res 1999 15 5647-5650. 

Oshima M, Dinchuk JE, Kargman SL, et al. Suppression of intestinal polyposis in APCA716 knockout mice by inhibition of cyclooxygenase 2 (COX-2). Cell 1996 87 803-809. 

---