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The effects of siguazodan, a selective phosphodiesterase inhibitor, on human platelet function
Author(s) -
Murray Kenneth J.,
England Paul J.,
Hallam Trevor J.,
Maguire Joanne,
Moores Kitty,
Reeves Martin L.,
Simpson Alec W. M.,
Rink Timothy J.
Publication year - 1990
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.1476-5381.1990.tb12978.x
Subject(s) - phosphodiesterase , platelet , chemistry , potency , phosphodiesterase inhibitor , vasodilation , pharmacology , platelet rich plasma , calcium , inotrope , endocrinology , enzyme , enzyme inhibitor , medicine , in vitro , biochemistry , biology , organic chemistry
1 The effects of siguazodan (SK&F 94836) a selective phosphodiesterase (PDE) inhibitor with inotropic and vasodilator activity, were studied on human platelets. 2 Siguazodan selectively inhibited the major cyclic AMP‐hydrolysing PDE in human platelet supernatants. The inhibited enzyme has been variously termed cyclic GMP‐inhibited PDE or PDE‐III. 3 In platelet‐rich plasma (PRP), siguazodan inhibited U46619‐induced aggregation more potently than that induced by ADP and collagen. Treatment of the PRP with aspirin had no effect on the potency of siguazodan. 4 In washed platelets, siguazodan increased cyclic AMP levels and reduced cytoplasmic free calcium ([Ca 2+ ] i ). ADP decreased the ability of siguazodan to raise cyclic AMP and this may explain its lower potency in inhibiting responses to ADP. 5 Siguazodan has anti‐platelet actions over the same concentration range that it is an inotrope and vasodilator.