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AH6809, a prostaglandin DP‐receptor blocking drug on human platelets
Author(s) -
Keery R.J.,
Lumley P.
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.tb11584.x
Subject(s) - platelet , chemistry , potency , receptor , pharmacology , prostaglandin , platelet aggregation inhibitor , platelet activating factor , whole blood , platelet aggregation , biological activity , antagonism , mechanism of action , prostacyclin , biochemistry , endocrinology , medicine , aspirin , in vitro , biology
1 The effect of AH6809 (6‐isopropoxy‐9‐oxoxanthene‐2‐carboxylic acid) has been studied upon the antiaggregatory and aggregatory actions of various agents on human platelets in whole blood. 2 Prostaglandin D 2 (PGD 2 ), BW245C, 9α,11β‐PGF 2 , PGI 2 and 5′‐N‐ethylcarboxamide adenosine (NECA) all inhibited ADP‐induced platelet aggregation in whole blood. The anti‐aggregatory activity of PGD 2 , BW245C and 9α,11β‐PGF 2 but not PGI 2 or NECA was antagonized by AH6809. NECA was antagonized by AH6809. 3 The antagonism of the anti‐aggregatory activity of PGD 2 by AH6809 was concentration‐related and could be overcome by increasing the concentration of PGD 2 . Analysis of the data yielded an apparent pA 2 for AH6809 of 5.35. 4 At approximately 10 fold higher concentrations than those required to antagonize the action of PGD 2 , AH6809 also antagonized the aggregatory effect of U‐46619 in whole blood (pA 2 = 4.45). However, concentrations of AH6809 up to 300 μ m were without effect upon either ADP‐ or platelet activating factor (Paf)‐induced aggregation (pA 2 < 3.5). 5 The potency of AH6809 against PGD 2 and U‐46619 was increased in a resuspended platelet preparation suggesting that the drug is extensively bound to plasma proteins. However, in resuspended platelets the specificity of AH6809 relative to that seen in whole blood was reduced since aggregation by ADP and Paf was also slightly antagonized. 6 In conclusion, AH6809 appears to be a weak but specific DP‐receptor blocking drug on human platelets and should prove to be a useful drug tool for defining the involvement of endogenous PGD 2 in platelet aggregation and classifying the mode of action of anti‐aggregatory prostanoids.