REV 5901: an orally effective peptidoleukotriene antagonist, detailed biochemical/pharmacological profile.

REV 5901 [alpha-pentyl-3-(2-quinolinylmethoxy)-benzene-methanol] has been shown to be a competitive antagonist of peptidoleukotrienes. In vitro it has a Ki value of 0.7 microM vs. [3H]leukotriene D4 ([3H]-LTD4) binding to membranes from guinea pig lung. Against LTC4-, LTD4- and LTE4-induced contractions of guinea pig parenchymal strips, it has Kb values of ca 3 microM and was relatively ineffective against contractions induced by other spasmogens. The peptiodoleukotriene-antagonist activity is also demonstrable against the hemodynamic and vasoconstriction effects of LTD4 in isolated guinea pig hearts. Oral antagonist activity has been shown with an LTD4-induced bronchoconstriction model and with an LTD4-induced wheal response model in guinea pigs. Unlike other reported antagonists, REV 5901 is ineffective against the multiple forms of cyclic nucleotide phosphodiesterases. Thus, in addition to its previously reported activity as a 5-lipoxygenase inhibitor, REV 5901 is a p.o. active antagonist of peptidoleukotrienes and represents a good tool for understanding the role of peptidoleukotrienes in disease.