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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

LY171883, 1-less than 2-hydroxy-3-propyl-4-less than 4-(1H-tetrazol-5-yl) butoxy greater than phenyl greater than ethanone, an orally active leukotriene D4 antagonist.

LY171883, 1-less than2-hydroxy-3-propyl-4-less than 4-(h-tetrazol-5-yl)butoxy greater than phenyl greater than ethanone, proved to be a potent antagonist of leukotriene (LT) D4 in guinea-pig ileum, trachea and lung parenchyma. The compound had little or no effect on contractions of isolated tissues to LTB4, prostaglandin F2 alpha, serotonin, histamine, bradykinin or carbamycholine. Responses of trachea to U46619, a thromboxane A2 mimetic, were antagonized by LY171883, but the doses required were approximately 10-fold higher than those necessary to produce the same degree of antagonism against LTD4. U46619 produced weak ileal contractions that were not blocked by LY171883. LY171883 antagonized both LTD4- and antigen-induced increases in total pulmonary resistance in anesthetized guinea pigs. LTD4 given intradermally to guinea pigs caused vascular leakage which was suppressed by prior administration of LY171883. LTC4-induced contractions of isolated ilea were only minimally antagonized by LY171883 whereas this agent reduced LTC4-evoked increases in total pulmonary resistance. Trachea contracted by LTD4 were relaxed by LY171883. Likewise, trachea contracted by either histamine or carbamylcholine were relaxed by LY171883 suggesting that this compound has airway smooth muscle relaxing properties. In vivo experiments supported these observations. In concert with these findings, biochemical studies showed LY171883 to be a potent inhibitor of phosphodiesterase obtained from human polymorphonuclear leukocytes and various guinea-pig tissues. This pharmacologic analysis indicates that LY171883, or a congener, may be of therapeutic value in asthma and in disease states characterized by an overproduction of LTD4.[1]

References

  1. LY171883, 1-less than 2-hydroxy-3-propyl-4-less than 4-(1H-tetrazol-5-yl) butoxy greater than phenyl greater than ethanone, an orally active leukotriene D4 antagonist. Fleisch, J.H., Rinkema, L.E., Haisch, K.D., Swanson-Bean, D., Goodson, T., Ho, P.P., Marshall, W.S. J. Pharmacol. Exp. Ther. (1985) [Pubmed]
 
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