Anti-inflammatory agents, inhibition

Inhibition of prostaglandin synthesis The synthesis of prostaglandins can be inhibited by a number of unrelated compounds. For example, Cortisol (a steroidal anti-inflammatory agent) inhibits phospholipase As activity (see Figure 17.23) and, therefore, the precursor of the prostaglandins, arachidonic acid, is... 

Two commonly used models to detect anti-inflammatory activity are carrageenan-induced paw edema and adjuvant-induced polyarthritis in rats. The former represents an acute and the latter a chronic inflammatory process. Non-steroidal anti-inflammatory agents inhibit the formation of carrageenan-induced paw edema. However, to detect activity in the developing and established phases of chronic inflammation, the polyarthritis model is well accepted. In both tests the measured endpoint is volume of the hind paw. This is done by immersing the hind paw in the well of a mercury displacement... 

Brouet, I. and Ohshima, H. 1995. Curcumin, an anti-tumour promoter and anti-inflammatory agent, inhibits induction of nitric oxide synthase in activated macrophages. Biochem. Biophys. Res. Commun., 206 533-540. 

Ebselen is a seleno-oiganic that mimics glutathione peroxidase and inhibits iron-stimulated lipid peroxidation. It significandy reduced both inferct size and oedema progression in the middle cerebral artery exclusion (MCAO) focal model of stroke in tats (Matsui et al. 1990). Ebselen has also been shown to be an effective anti-inflammatory agent in a H202-dependent inflammation model in tats (Parnham 1991). 

Cromolyn and nedocromil are inhaled anti-inflammatory agents that block both the early- and late-phase response. Both agents are considered alternative therapies to inhaled corticosteroids for the treatment of mild persistent asthma however, both are less effective than low doses of inhaled corticosteroids.2,30 The exact mechanism of action of these agents is not understood, but they appear to inhibit mast cell mediator release as well as modulate other inflammatory responses.3... 

Inhibition of leucocyte adhesion to endothelium. By acting on the gene transcription factor called nuclear factor kappa B (NFkB), NO limits the expression by endothelial cells of monocyte chemotactic protein-1 (MCP-1) and VCAM-1. As both MCP-1 and VCAM-1 are involved with pro-inflammatory responses, NO is in this manner an anti-inflammatory agent ... 

Davenport CJ, Morgan KT. 1989. Inhibition of methyl iodide neurotoxicity in vitro by the anti-inflammatory agent BW755C [Abstract], Toxicologist 9 148. 

MTX also has several effects on the purine synthetic pathway. MTXPGs inhibit the enzyme aminoimidazole carboxamide ribonucleotide (AlCAR) transformylase, which in turn causes intracellular accumulation of AICAR. AICAR and its metabolites can then inhibit two enzymes in the adenosine pathway adenosine deaminase and adenosine monophosphate (AMP) deaminase, which leads to intracellnlar accumulation of adenosine and adenine nucleotides. Subsequent dephosphorylation of these nucleotides results in increased extracellular concentrations of adenosine, which is a powerful anti-inflammatory agent (11). 

Conklyn, M. J., Kadin, S. B., and Showell,H. J. (1990) Inhibition of IgE-mediated A-acetylglucosaminidase and serotonin release from rat basophilic leukemia cells (RBL-2H3) by Tenidap A novel anti- inflammatory agent. Int. Arch. Allerg. Appl. Immunol. 91, 369-373. 

Pak, J.Y. Gildehaus, D., Miyashiro, J.M., Penning, T.D., Seibert, K., Isakson, P.C., and Stallings, W.C. Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents. Nature... 

Indometacin, which is a non-steroidal anti-inflammatory drug, inhibits the enzyme cyclo-oxygenase implicated in inflammatory reactions. Indometacin is more effective as an anti-inflammatory agent than ibuprofen and tends to have a higher side-effect profile, including headache, diarrhoea and gastrointestinal disturbances. Rectal administration reduces but does not prevent gastrointestinal tract disturbances. 

Acetaminophen differs from the nonsteroidal anti-inflammatory agents described in that it is devoid of anti-inflammatory and antirheumatic properties. It was recently shown that acetaminophen, like aspirin, inhibits cyclooxygenase action in the brain and is even stronger than aspirin. On the other hand, the mechanism of analgesic action of acetaminophen is not fully clear, since it acts poorly on peripheral cyclooxygenase. 

Pharmacology Nedocromil is an inhaled anti-inflammatory agent for the preventive management of asthma. It inhibits the in vitro activation of, and mediator release from, a variety of inflammatory cell types associated with asthma, including eosinophils, neutrophils, macrophages, mast cells, monocytes and platelets. Nedocromil inhibits the development of early and late bronchoconstriction responses to inhaled antigen. 

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