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Eosinophil phosphodiesterase

Tetrahydropyrazolo[3,4-f]pyridines have been prepared as cannabinoid modulators <2007W0112399>. The pyra-zolo[3,4-4pyridine, Apixaban (BMS-562247), has been found to be a highly potent, selective, efficacious, and orally bioavailable inhibitor of blood coagulation factor xa <2007JMC5339>. Several pyrazolo[3,4-f]pyridines have been found to be potent inhibitors of human eosinophil phosphodiesterase <2007JMC344>. [Pg.487]

Theophylline appears to produce bronchodilation by inhibiting phosphodiesterases, which may also result in antiinflammatory and other nonbronchodilator activity through decreased mast cell mediator release, decreased eosinophil basic protein release, decreased T-lymphocyte proliferation, decreased T-cell cytokine release, and decreased plasma exudation. [Pg.929]

The xanthine theophylline has been used for several decades in the treatment of asthma. This compound produces different effects at the cellular level, including phosphodiesterase isoenzyme inhibition, adenosine antagonism, catecholamine secretion enhancement, and the modulation of calcium fluxes. Recently, theophylline was found to have both immunomodulatory and anti-inflammatory properties therefore, interest in its use in patients with asthma has been renewed [103]. Recent studies have thus discovered that at low doses, theophylline is able to decrease airway inflammation, accelerate eosinophil apoptosis, and decrease recruitment of lymphocytes and neutrophils to the lungs. Although it is classified as a phosphodiesterase inhibitor, its exact therapeutic mechanism of action remains undetermined [104]. Of the new mechanisms that have been included in the potential mode of action of theophylline, one is the apoptosis of inflammatory cells. In eosinophils and lymphocytes, for example, this effect is due to the compound s ability to inhibit phosphodiesterase, which leads to an even more pronounced increase in intracellular cAMP levels than that which occurs when adenylate cyclase, the enzyme that synthesizes cAMP, is activated. This inhibition and the resulting cAMP level increase thus lead to... [Pg.163]

Eosinophil infiltration in the bronchoalveolar lavage fluid in guinea pigs was induced by recombinant human IL-8 (Lagente et al. 1995). Administration of the phosphodiesterase IV isoenzyme inhibitor, rolipram (5 mg/kg) or betamethasone (10 mg/kg) significantly P <0.05) reduced the IL-8-induced eosinophil infiltration in bronchoalveolar lavage fluid. Betamethasone may act directly on eosinophils to inhibit their infiltration by IL-8. [Pg.266]


See other pages where Eosinophil phosphodiesterase is mentioned: [Pg.765]    [Pg.211]    [Pg.765]    [Pg.211]    [Pg.103]    [Pg.1307]    [Pg.529]    [Pg.99]    [Pg.114]   
See also in sourсe #XX -- [ Pg.211 ]




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