Effects of a thromboxane synthetase inhibitor and a cAMP phosphodiesterase inhibitor, singly and in combination, on platelet behaviour.
The effects of dazoxiben, a thromboxane synthetase inhibitor, and AH-P 719, a cAMP phosphodiesterase inhibitor, on arachidonic acid (AA)-induced platelet behaviour were determined. The levels of cAMP present in platelet-rich plasma (PRP) after stimulating the platelets with AA in the absence and presence of the agents were also measured. AH-P 719, as well as dazoxiben, was more effective as an inhibitor of AA-induced platelet behaviour in PRP from some individuals than in PRP from others, and the effectiveness with which it inhibited platelet behaviour paralleled that of dazoxiben. A combination of both agents was more effective than either agent alone. Both AH-P 719 and dazoxiben increased the level of cAMP in AA-stimulated platelets but again they were more effective in PRP from some individuals than others. A combination of AH-P 719 and dazoxiben always resulted in higher levels of cAMP than either agent alone. These results imply that cAMP is involved in determining the effects of thromboxane synthetase inhibitors on platelet behaviour, and indicate that the anti-thrombotic potential of a combination of a thromboxane synthetase inhibitor and a cAMP phosphodiesterase inhibitor may be greater than that of the individual agents.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D000242:Cyclic AMP / Q000097:blood; D004347:Drug Interactions; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D010974:Platelet Aggregation / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D001095:Arachidonic Acids; D007093:Imidazoles; C029166:dazoxiben; C049655:4-(2-(1-imidazolyl)ethoxy)benzoic acid; D016718:Arachidonic Acid; D012701:Serotonin; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D013930:Thromboxane-A Synthase