LY83583, a quinolinedione, and LY1 51 364, a quinoxalinedione, were developed as inhibitors of leukotriene(slow reacting substance of anaphylaxis) release. They preferentially inhibited the release of leukotrienes over histamine from fragmented guineapig lung and rat peritoneal cells in vitro, regardless of whether the mediators were released immunologically by antigen or chemically by the divalent cationic ionophore, A231 87. Similar results were obtained with rat pentoneal cells in vivo. In that system, comparison of LY83583 with disodium cromoglycate showed theformer to preferentially inhibit release of leukotrienes, whereas the latter favored inhibition of histamine release.

LY83583 did not significantly decrease antigen-induced bronchospasm in guinea pigs after iv administration of doses that approached toxic levels. In addition, LY83583 did not antagonize contractions to carbachol or histamine on guinea-pig trachea, prostaglandin F2aldt6d contraction on guinea-pig ileum or contractions produced by serotonin on guinea-pig aorta. This agent, at 1 x 10-M, reduced the maximal responses to bradykinin on ileum and caused a nghtward displacement with a reduction in the maximal response to norepinephnne on guinea-pig aorta. In summary, LY83583 and LY1 51 364 have interesting pharmaco-logic profiles which make them useful as tools in understanding the role of the leukotnenes in isolated tissue systems.