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PA 2 values for antagonists of platelet activating factor on aggregation of rabbit platelets
Author(s) -
O'Donnell Stella R.,
Barnett Christopher J.K.
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.tb11545.x
Subject(s) - platelet activating factor , schild regression , platelet , chemistry , antagonist , dissociation constant , pharmacology , stereochemistry , receptor , medicine , endocrinology , biochemistry , biology
1 The relative potencies, and equilibrium dissociation constants, for nine antagonists of platelet activating factor (Paf) have been determined on rabbit platelets (in diluted platelet‐rich plasma (PRP)) in experiments in which the aggregatory response to Paf was measured. 2 Log concentration‐response (% maximum) curves to Paf were obtained in the absence (controls) and presence of different concentrations of each Paf antagonist drug. The antagonists shifted the Paf curves to a higher concentration range and the slopes of the Schild plots, constructed from these data, suggested that the drugs were competitive antagonists of Paf. The slopes of the Schild plots for CV‐3988 and SRI 63–119 were > 1. 3 The pA 2 values (pK B values in parentheses) were: WEB 2086 7.31 (7.63); SRI 63–119 6.95; L‐652,731 6.71 (6.73); BN 52021 6.38 (6.47); SRI 63–072 6.36 (6.43); CV‐3988 5.87; 48740 RP 4.97 (5.07); ketotifen 4.94 (4.95); thiazinamium 4.73 (4.76). 4 This study provides, for the first time, some functional response data for Paf antagonists (pK B values) which are in an appropriate form for use in classifying putative Paf receptors. The study also provides the comparative potencies of these Paf antagonists in inhibiting Paf‐induced platelet aggregation. WEB 2086 was the most potent of the drugs examined.