The Promise Introduction of selective cyclooxygenase (COX)-2 inhibitors held a promise of improved treatment of arthritis without the gastrointestinal effects associated with aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), which effect both COX-1 and COX-2 activity. Celecoxib, etodolac, meloxicam, and rofecoxib are classified as selective COX-2 inhibitors. Initial placebo and l...

Glutamate/N-methyl-d-aspartate (NMDA) receptor-mediated neurotoxicity involves cyclooxygenase (COX)-2. We demonstrate that this neurotoxicity reflects activation of COX-2 by S-nitrosylation after selective binding of neuronal nitric oxide synthase (nNOS) to COX-2. nNOS, via its PDZ domain, binds COX-2 with the generated NO S-nitrosylating and activating the enzyme. Selective disruption of nNOS-...

We report data from two related assay systems (isolated enzyme assays and whole blood assays) that C-phycocyanin a biliprotein from Spirulina platensis is a selective inhibitor of cyclooxygenase-2 (COX-2) with a very low IC(50) COX-2/IC(50) COX-1 ratio (0.04). The extent of inhibition depends on the period of preincubation of phycocyanin with COX-2, but without any effect on the period of prein...

James Mitchell trained in anaesthesia at St Vincent’s Hospital, Melbourne. Subsequently, he spent three years as an Assistant Professor in the Department of Anesthesia at the University of California San Francisco, where his research work focused on the role of prostaglandins and leukotrienes in mechanisms of inflammation and his clinical work was predominantly in neuroanaesthesia. In 2004, he ...

Effects of multiple-dose regimens (oral, daily, once a day for 15 days) cyclooxygenase (COX) inhibitors etoricoxib (1 and 10 mg/kg), diclofenac sodium 5 mg/kg) their combinations with 2-ethyl-6-methyl-3-hydroxypyridine succinate (mexidol 25 on rat behavior were studied in the open field test, rotarod test elevated plus maze test. Exploratory (in test) locomotor rats was significantly weakened o...

The energetics and models of COX-2 complexed with nonsteroidal anti-inflammatory drugs (NSAIDs) having different degrees of selectivity for two isoforms of COX (COX-2 and COX-1) have been studied using computer modelling approach. The models are obtained for complexes of NS398 (NS), a selective COX-2 inhibitor; indoprofen (Ind), a non-selective inhibitor; di-tert-butylbenzofurans (DHDMBFs) with...

It is well-established that prostaglandins (PGs) affect tumorigenesis, and evidence indicates that PGs also are important for the reduced food intake and body weight loss, the anorexia-cachexia syndrome, in malignant cancer. However, the identity of the PGs and the PG producing cyclooxygenase (COX) species responsible for cancer anorexia-cachexia is unknown. Here, we addressed this issue by tra...

PURPOSE To assess the risk of gastrointestinal perforation, ulcers, or bleeding (PUB) associated with the use of conventional nonsteroidal anti-inflammatory drugs (NSAIDs) with proton pump inhibitors (PPIs) and selective COX-2 inhibitors, with or without PPIs compared with conventional NSAIDs. METHODS A case-control study was performed within conventional NSAIDs and/or selective COX-2 inhibit...

Treatment with non-steroidal anti-inflammatory drugs, either non-selective or selective cyclooxygenase-2 (COX-2) inhibitors, consistently impairs ovulation, indicating the essential role of COX-2/prostaglandins in the ovulatory process. Indomethacin, a potent inhibitor of both COX-1 and COX-2, induced several ovulatory alterations, consisting of a decrease in the number of oocytes effectively o...

PURPOSE NSAIDs constitute an important class of drugs with therapeutic applications that have spanned several centuries. Treatment of inflammatory conditions such as rheumatoid arthritis (RA) and osteoarthritis (OA) starting from the classic drug aspirin to the recent rise and fall of selective COX-2 inhibitors has provided an enthralling evolution. Efforts to discover an ultimate magic bullet ...