(2-cyano-3-(methylamino)phenyl)oxoacetic-acid-sodium-salt and Hypersensitivity

[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.

Topics: Amino Acids; Animals; Antibody Formation; Bronchi; Capillary Permeability; Dogs; Female; Guinea Pigs; Histamine Release; Hypersensitivity; In Vitro Techniques; Male; Muscle Contraction; Oxamic Acid; Passive Cutaneous Anaphylaxis; Phosphodiesterase Inhibitors; Rats; Rats, Inbred Strains; Trachea

Topics: Administration, Oral; Amino Acids; Animals; Hypersensitivity; Male; Oxamic Acid; Passive Cutaneous Anaphylaxis; Rats; Structure-Activity Relationship