Synergistic Antiplatelet Effect of Ridogrel, a Combined Thromboxane Receptor Antagonist and Thromboxane Synthase Inhibitor, and UDCG-212, a cAMP-Phosphodiesterase Inhibitor

1993 ◽  
Vol 70 (05) ◽  
pp. 822-825 ◽  
Author(s):  
B Hoet ◽  
J Arnout ◽  
H Deckmyn ◽  
J Vermylen
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Receptor Antagonist ◽  
Phosphodiesterase Inhibitor ◽  
Camp Phosphodiesterase ◽  
Thromboxane Receptor ◽  
Thromboxane Synthase Inhibitor ◽  
Thromboxane Receptor Antagonist ◽  
Synthase Inhibitor ◽  
Camp Levels

SummaryRidogrel, a combined thromboxane receptor antagonist and thromboxane synthase inhibitor (1), inhibits platelet aggregation. Following stimulation with arachidonic acid, cAMP-levels are increased in human platelets preincubated with ridogrel, this is due to the known reorientation of the metabolism of the formed endoperoxides towards adenylate cyclase stimulating prostaglandins.Pretreatment of resting platelets with UDCG-212, a cAMP-phosphodiesterase inhibitor (2), also inhibits platelet aggregation induced by arachidonic acid, concomitant with an increase in cAMP levels, due to an inhibition of its breakdown. Under basal conditions, cAMP also is increased.By combining the two drugs, a more than additive action was observed on platelet aggregation and on both resting and stimulated platelet cAMP content. The appropriate combination may result in a more effective antiplatelet strategy.

scholarly journals Pharmacology of the Thromboxane Receptor Antagonist and Thromboxane Synthase Inhibitor BM-531

2006 ◽  
Vol 19 (2) ◽  
pp. 87-96 ◽  
Author(s):  
Jean-Michel Dogné ◽  
Stéphanie Rolin ◽  
Xavier Leval ◽  
Patricia Benoit ◽  
Philippe Neven ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Thromboxane Synthase ◽  
Thromboxane Receptor ◽  
Thromboxane Synthase Inhibitor ◽  
Thromboxane Receptor Antagonist ◽  
Synthase Inhibitor

Effects of OKY 1581 on bronchoconstrictor responses to arachidonic acid and PGH2

1987 ◽  
Vol 62 (5) ◽  
pp. 2066-2074 ◽  
Author(s):  
S. J. Tilden ◽  
D. C. Underwood ◽  
K. H. Cowen ◽  
M. J. Wegmann ◽  
G. B. Graybar ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Transpulmonary Pressure ◽  
Substantial Part ◽  
Synthesis Inhibitor ◽  
Intravenous Injections ◽  
Thromboxane Receptor ◽  
Thromboxane Synthase Inhibitor ◽  
Airway Responses ◽  
Thromboxane Receptor Antagonist ◽  
Synthase Inhibitor

The influence of OKY 1581, a thromboxane synthase inhibitor, on airway responses to arachidonic acid and endoperoxide, [prostaglandin (PG) H2], were investigated in anesthetized, paralyzed, mechanically ventilated cats. Intravenous injections of arachidonic acid and PGH2 caused dose-related increases in transpulmonary pressure and lung resistance and decreases in dynamic and static compliance. OKY 1581 significantly decreased airway responses to arachidonic acid but not to PGH2. Sodium meclofenamate, a cyclooxygenase inhibitor, abolished airway responses to arachidonic acid but had no effect on airway responses to PGH2. OKY 1581 or meclofenamate has no effect on airway responses to PGF2 alpha, PGD2, or U 46619, a thromboxane mimic. In microsomal fractions from the lung, OKY 1581 inhibited thromboxane formation without decreasing prostacyclin synthesis or cyclooxygenase activity. These studies show that OKY 1581 is a selective thromboxane synthesis inhibitor in the cat lung and suggest that a substantial part of the bronchoconstrictor response to arachidonic acid is due to thromboxane A2 formation. Moreover, the present data suggest that airway responses to endogenously released and exogenous PGH2 are mediated differently and that a significant part of the response to exogenous PGH2 may be due to activation of an endoperoxide/thromboxane receptor, since responses to PGH2 are blocked by the thromboxane receptor antagonist SQ 29548.

Sign in / Sign up

Export Citation Format

Share Document