Leukotriene antagonists and inhibitors as modulators of IgE-mediated reactions

The biological activities of the leukotrienes and the fact that they are produced in elevated amounts in asthmatic subjects are consistent with their playing a role in IgE-mediated diseases. Clinical trials of results obtained with potent leukotriene D4 receptor antagonists such as MK-571, MK-679 and ICI 204,219 are consistent with leukotriene D4 receptor activation being a central feature of the disease. Such receptor antagonists will also be of use in defining the role of leukotriene D4 receptor activation in other IgE-mediated human diseases such as allergic conjunctivitis and allergic rhinitis. The role of leukotriene B4 in diseases mediated through IgE reactions remains to be defined. First generation leukotriene biosynthesis inhibitors such as Zileuton and MK-886 have not shown efficacy comparable to potent leukotriene D4 receptor antagonists, consistent with the fact that they have not been fully effective at suppressing leukotriene production in man. It will clearly be of interest to test more potent leukotriene biosynthesis inhibitors such as ICI D2318 and MK-0591 in chronic IgE-mediated diseases and compare the results with those already obtained with leukotriene D4 receptor antagonists.