RESUMO
Nonsteroidal anti-inflammatory drugs (NSAID's) and other antirheumatic compounds such as disease modifying antirheumatic drugs (DMARD's), immunosuppressives and glucocorticoids were tested to determine if daily medication for two weeks could elevate subnormal levels of plasma iron in adjuvant-arthritic (AA) rats. Aspirin, indomethacin, ibuprofen and phenylbutazone were chosen as representative carboxylic acids and pyrazole NSAID's. Although NSAID's at all doses significantly reduced noninjected paw swelling, no NSAID significantly enhanced subnormal plasma iron levels in AA rats. In contrast, the standard DMARD's auranofin and gold sodium thiomalate, as well as the glucocorticoid, dexamethasone and the immunosuppressives, methotrexate and cyclosporin-A all significantly restored plasma iron levels 28 to 100 percent. Plasma iron depression, a parameter of the acute phase response probably under regulation by pro-inflammatory cytokines, is not reversed by NSAID treatment. This appears to be a useful method for distinguishing NSAID's from other anti-arthritic compounds.
Assuntos
Anti-Inflamatórios/uso terapêutico , Artrite Experimental/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite , Artrite Experimental/sangue , Feminino , Glucocorticoides/uso terapêutico , Imunossupressores/uso terapêutico , Ferro/sangue , RatosRESUMO
Replacement of the carboxyl group of 2-(3-benzoylphenyl)propionic acid (Ketoprofen) with various bulky amines has produced a series of highly active antiinflammatory agents that have reduced intestinal ulcerogenicity and have better therapeutic ratios in the 21-day adjuvant arthritis assay in rats than currently marketed nonsteroidal antiinflammatory drugs. Activity is maintained on reduction of these 2-(3-benzoylphenyl)propyl bulky amines to the corresponding alcohols or methylene analogues, on conversion of the ketone function to a primary amine or oxime, and on introduction of a 4-halo substitutent (Cl or F) on the terminal aromatic ring. Removal of the alpha-CH3 group greatly reduces the antiinflammatory activity of the series. These compounds have been synthesized by the reductive amination of 2-(3-bromophenyl)propionaldehyde with the respective amine followed by lithiation of this product and condensation with the appropriate benzonitrile.