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Effect of a Paf antagonist, WEB 2086, on airway microvascular leakage in the guinea‐pig and platelet aggregation in man
Author(s) -
Evans Timothy W.,
Dent Gordon,
Rogers Duncan F.,
Aursudkij Boonrut,
Chung K. Fan,
Barnes Peter J.
Publication year - 1988
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1988.tb11511.x
Subject(s) - antagonist , guinea pig , platelet activating factor , airway , platelet aggregation , pharmacology , medicine , chemistry , platelet , anesthesia , receptor
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 (IC 50 = 117 ± 35 n m , 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.