Kinetics of action of two leukotriene antagonists on guinea pig ileum

Abstract

The kinetics of action of two selective leukotriene (SRS-A) antagonists, FPL 55712 and FPL 59257, on guinea pig isolated ileum were examined by measuring pA2, pD'2 and the rate constants K1, K2, Ke and Kon. FPL 55712 was shown to be a competitive antagonist, producing a parallel displacement of dose response curves to LTD4 with no depression of the maximum. FPL 59257, however, was shown to be a non-competitive antagonist which depressed the maximum response to LTD4 and yielded a Schild plot slope significantly less than unity. FPL 59257 has a slower onset and greater duration of action than FPL 55712, as reflected in the rate constants K2 and Kon. The implications of these results are discussed.