Effect of a Paf antagonist, WEB 2086, on airway microvascular leakage in the guinea‐pig and platelet aggregation in man

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Abstract
1 The triazolodiazepine WEB 2086 has been evaluated as an antagonist of platelet-activating factor (Paf) by studying its effects on Paf-induced human platelet aggregation and microvascular leakage in guinea-pigs. 2 WEB 2086 inhibited Paf-induced platelet aggregation in platelet-rich plasma in vitro (IC50 = 117 ± 35 nm, mean ± s.d.) but had no effect on adenosine 3′,5′-diphosphate-induced aggregation. 3 Paf-induced microvascular leakage, measured by the extravasation of intravenously-injected Evans blue dye, was inhibited in a dose-related fashion in the airways and other tissues by WEB 2086, achieving a maximal inhibitory effect at 10 μg kg−1, i.v. 4 However, WEB 2086 (10 μg kg−1, i.v.) did not inhibit a comparable increase in vascular permeability induced by ovalbumin in sensitized guinea-pigs. 5 We conclude that WEB 2086 is a potent antagonist of Paf and that Paf does not appear to be responsible for antigen-induced microvascular leakage.