Cyclooxygenase 1/2 inhibitors Cyclooxygenases

Tegeder I, Pfeilschifter J, Geisslinger G (2001) Cyclooxygenase-independent actions of cyclooxygenase inhibitors. FASEB J 15 2057-2072... 

Tegeder I, Geisslinger G (2006) Cardiovascular risk with cyclooxygenase inhibitors general problem with substance specific differences Naunyn Schmiedebergs Arch Pharmacol 373 1—17... 

Unlike aspirin and other cyclooxygenase inhibitors that work on the COX-1 and COX-2 enzymes, acetaminophen works on the COX-3 enzyme, which is present in the spinal column and brain. This helps it to avoid shutting down prostaglandin function elsewhere in the body, which is why it has no anti-inflammatory effects and does not affect blood platelets or the stomach lining. 

Like aspirin, ibuprofen is a nonsteroidal anti-inflammatory drug. It is a cyclooxygenase inhibitor that interferes with COX-1 and COX-2 forms of that enzyme. Its effects on COX-2 give it fever-reducing (antipyretic), analgesic (pain relief), and anti-inflammatory functions. 

Williams, JH and Bliss, TV (1989) An in vitro study of the effect of lipoxygenase and cyclooxygenase inhibitors of arachidonic acid on the induction and maintenance of long-term potentiation in the hippocampus. Neurosci. Lett. 107 301-309. 

Cyclooxygenase Inhibitors. The synthesis of prostaglandin and thromboxane has been linked with multiple organ failure in animals and humans with sepsis. Bernard et al. (B18) reported the results of a large trial of the cyclooxygenase inhibitor ibuprofen in patients with sepsis. Treatment for 48 hours with... 

Drugs that target other sites of platelet action include thromboxane synthetase inhibitors, serotonin or 5-hydroxytryptamine (5-HT2) receptor blockers, and thromboxane A2 receptor blockers, in addition to cyclooxygenase inhibitors and prostaglandin analogues. 

Imidazopyridazines DM1 (16) and DM2 (17), originally prepared as cyclooxygenase inhibitors, have demonstrated T-type antagonist properties in voltage clamp studies using the Cav3.1 subtype, as well as seizure suppression in WAG/Rij rats at 1, 3, and 10 mg/kg. The potency of these compounds toward the block of other ion channels was not reported [58]. 

Several interesting findings dealing with 2-quinolinylmethyl esters related to Rev 5901A (139) have been reported. Workers at Wyeth-Ayerst found that attachment of this moeity to a number of classical NSAIDs endowed these cyclooxygenase inhibitors with 5-LO inhibitory activity in cell assays... 

Box 11.6 Ancient and modern cyclooxygenase inhibitors chronic pain and gastric injury, and myocardial infarction... 

The lability of benzylic positions to cytochrome P450 metabolism has been exploited to decrease the unacceptably low clearance and resultant long half-life of various compounds. For example celecoxib, a selective cyclooxygenase inhibitor, has a half-life of 3.5 h in the rat. Early structural leads, represented by compoimds in... 

Shiff SJ, Shivaprasad P, Santini DL. Cyclooxygenase inhibitors drugs for cancer prevention. Curr Opin Pharmacol 2003 3 352-61. 

Far out the most important agent in this group is aspirin, a cyclooxygenase inhibitor which is discussed in more detail in Chapter 26. Its unique properties as a platelet aggregation inhibitor are brought forward by the fact that while platelet cyclooxygenase is irreversibly inhibited at low doses of aspirin the synthesis in endothelium of prostacyclin, a platelet aggregation inhibitor itself, recovers more quickly. 

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