RESUMO
[2-Cyano-3-(methylamino)phenylamino]oxoacetic acid, sodium salt (Wy-41,195) was found to be a potent oral inhibitor (viz., ED50, 0.3 mg/kg) of IgE-mediated release in the rat passive cutaneous anaphylaxis (PCA) model and was very effective by the aerosol and oral route in the rat passive lung anaphylaxis model. High doses (25-50 mg/kg p.o.) were effective when administered up to 180 min before antigen challenge in the rat PCA model. The compound had minimal phosphodiesterase activity and demonstrated no bronchodilator or antihistamine activity. In the dog, Wy-41,195 inhibited histamine-induced reflex bronchoconstriction but had little effect on Ascaris-induced bronchoconstriction. No significant ancillary pharmacology was observed for Wy-41,195 except for inhibition of gastric secretion in the rat. The compound is relatively nontoxic and possesses a very high therapeutic index (greater than 10 000). Activity in these animal systems indicates that Wy-41,195 may hold promise in the treatment of bronchial asthma and other allergic diseases in man.
Assuntos
Aminoácidos , Hipersensibilidade/tratamento farmacológico , Ácido Oxâmico/análogos & derivados , Animais , Formação de Anticorpos/efeitos dos fármacos , Brônquios/efeitos dos fármacos , Permeabilidade Capilar/efeitos dos fármacos , Cães , Feminino , Cobaias , Liberação de Histamina/efeitos dos fármacos , Técnicas In Vitro , Masculino , Contração Muscular/efeitos dos fármacos , Ácido Oxâmico/farmacologia , Anafilaxia Cutânea Passiva/efeitos dos fármacos , Inibidores de Fosfodiesterase , Ratos , Ratos Endogâmicos , Traqueia/efeitos dos fármacosRESUMO
Delayed hypersensitivity (DH) was induced in the footpads of mice sensitized to methylated bovine serum albumin (MBSA). The magnitude of this DH response increased with increasing sensitizing concentration of MBSA. Levamisole administered 1 hr prior to MBSA challenge stimulated the DH response and this was optimal using subliminal sensitizing concentrations of antigen. A number of antirheumatic agents, immunomodulators mediator antagonists and antiallergics were subsequently examined using the subliminal sensitizing concentration of MBSA. The same drugs were also evaluated using a normal sensitizing procedure. These studies indicate that the sensitizing concentration of antigen is critical in establishing whether a drug will stimulate or suppress a DH response.
