Van Wauwe, J.P. and J.G. Goossens: Dextran-induced edema formation in mouse ear: A pharmacological evaluation. Drug Dev. Res. 8:213-218, 1986. Intravenous injection of dextran T500 and pontamine sky-blue dye into mice results in increased vascular permeability and edema formation, characterized by an intense blueing of the ears. By determining the amount of extravasated dye, we compared a number of S2-serotonin antagonists, Hi-and H2-antihistamines, anticholinergics, and inhibitors of arachidonic acid metabolizing enzymes for their effects on ear edema. All S2-antagonists tested (cinanserin, cyproheptadine, ketanserin, and ritanserin) dose-dependently suppressed ear blueing. Some HI-antihistamines (astemizole and azatadine) were also inhibitory, but other Hi-antagonists (brompheniramine, chlorpheniramine, levocabastine, and pyrilamine) failed to weaken the reaction. The anti-dextran activity of the HI-blockers seemed to be related to their ability to abolish serotonin-induced vascular permeability of the mouse ear. Of the compounds interfering with arachidonic acid metabolizing enzymes, only BW 755C, a lipoxygenase inhibitor, proved active. The cyclo-oxygenase inhibitors indomethacin and suprofen, the thromboxane synthetase inhibitor dazoxiben, the H2-antagonists cimetidine and ranitidine, and the anticholinergics isopropamide and hexamethonium were inactive. These data provide evidence that the dextran-induced edema formation in mouse ear is predominantly mediated by serotonin, but they also suggest a participating role for a lipoxygenase-derived arachidonic acid metabolite(s).