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

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. WEB 2086 inhibited Paf‐induced platelet aggregation in platelet‐rich plasma in vitro (IC 50 = 117 ± 35 n m , mean ± s.d.) but had no effect on adenosine 3′,5′‐diphosphate‐induced aggregation. 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. 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. 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.