Eicosanoid receptor antagonists

In a human lung epithelial cell line, in which histamine increased the intracellular calcium concentration and the formation of eicosanoids, this response was antagonized by the histamine Hi receptor antagonist diphenhydramine but unaffected by the H2 receptor antagonist cimetidine. Fenspiride inhibited Hi receptor-induced calcium increase. Histamine also caused a biphasic increase in arachidonic acid release, which was inhibited by fenspiride. This study suggests a further mechanism that would promote antiinflammatory and bronchodilator properties. 

The major eicosanoids are products of 0)-6 essential fatty acids, and the essentiality of this group of fatty acids relates primarily to their functions as eicosanoids. Both the prostanoids and the leukotrienes (LTs) were discovered as vasoactive substances active on reproductive and pulmonary smooth muscle, respectively. The structures of the more stable prostanoids were determined in the late 1950s and early 1960s by workers at the Karolinksa Institute in Sweden and Unilever Laboratories in the Netherlands. The LTs were known initially as slow-reacting substances of anaphylaxis. Their structures were determined in the early 1980s. The details of the pathways and the enzymes and receptors for these pathways were characterized over the last 35 years. Because eicosanoid overproduction is associated with a number of pathologies, potent enzyme inhibitors and receptor antagonists have been developed that are widely used therapeutically. 

The thromboxane receptor antagonist S18SS6 but not aspirin inhibits athero genesis in apo E-deficient mice evidence that eicosanoids other than thromboxane contribute to atherosclerosis. 

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