Improvement of pulmonary function by oral treatment with a VLA-4 antagonist in a mouse asthmatic model

We investigated in vivo efficacies of the newly synthesized vla-4 antagonist compound a {trans-4-[1-[[2,5-dichloro-4-(1-methyl-3- indolylcarboxamido)phenyl]acetyl]-(4s)-methoxy-(2s)-pyrrolidinylmethoxy] cyclohexanecarboxylic acid} on ascaris antigen-induced airway inflammation and hyperresponsiveness in a murine asthmatic model. oral administration of compound a significantly inhibited eosinophil infiltration into balf and airway hyperresponsiveness 48 h after the antigen challenge. histologic analysis of the lung sections confirmed the balf result and revealed suppression of edema and mucus hyperplasia at 8 and 48 h after the challenge,respectively. these findings clearly show that orally active compound a has therapeutic potential for treatment of asthma. © the japanese pharmacological society.