The effects of siguazodan, a selective phosphodiesterase inhibitor, on human platelet function

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 v...

Full description

Saved in:
Bibliographic Details
Published in:British journal of pharmacology 1990-03, Vol.99 (3), p.612-616
Main Authors: Murray, Kenneth J., England, Paul J., Hallam, Trevor J., Maguire, Joanne, Moores, Kitty, Reeves, Martin L., Simpson, Alec W. M., Rink, Timothy J.
Format: Article
Language:English
Subjects:
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Adenosine Diphosphate - metabolism
Aspirin - pharmacology
Biological and medical sciences
Blood Platelets - drug effects
Blood Platelets - enzymology
Blood Platelets - metabolism
Calcium - metabolism
Cardiovascular system
Chromatography, Ion Exchange
Collagen - pharmacology
Cyclic AMP - metabolism
Guanidines - pharmacology
Humans
In Vitro Techniques
Medical sciences
Pharmacology. Drug treatments
Phosphodiesterase Inhibitors - pharmacology
Platelet Aggregation - drug effects
Platelet Aggregation Inhibitors - pharmacology
Platelet Function Tests
Prostaglandin Endoperoxides, Synthetic - pharmacology
Pyridazines - pharmacology
Vasodilator agents. Cerebral vasodilators
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 ([Ca2+]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.
ISSN:0007-1188
1476-5381
DOI:10.1111/j.1476-5381.1990.tb12978.x