Mechanism of action of dipyridamole.
Dipyridamole appears to act in vivo by synergistically modifying several biochemical pathways, including: a) inhibition of platelet cAMP-phosphodiesterase; b) potentiation of adenosine inhibition of platelet function by blocking reuptake by vascular and blood cells, and subsequent degradation of adenosine; and possibly, c) potentiation of PGI2 antiaggregatory activity and enhancement of PGI2 biosynthesis. These independent processes inhibit platelet function by increasing platelet cAMP through both a reduction in enzymatic cAMP-degradation, and stimulation of cAMP formation via activation of adenylcyclase by adenosine and possibly PGI2. Only the inhibition of cAMP phosphodiesterase appears to be involved in the dipyridamole inhibition of isolated platelets in vitro, since adenosine and PGI2 originate in vivo from tissues other than platelets and any blood concentrations existing in vivo will disappear before platelet-rich plasma has been prepared for in vitro platelet studies. The antithrombotic effects of dipyridamole in a baboon model of arterial thromboembolism are unaffected by simultaneous administration of dazoxiben, a specific thromboxane synthetase inhibitor, but are optimally potentiated by the simultaneous addition of aspirin in doses of 20 mg/kg/day. Since this dose of aspirin has no detectable antithrombotic effects when used alone, but blocks vascular PGI2 synthesis, the antithrombotic effects of dipyridamole, at least in this model, appear to be independent of prostacyclin.
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects; D004176:Dipyridamole / Q000494:pharmacology*; D011464:Epoprostenol / Q000494:pharmacology; D005340:Fibrinogen / Q000378:metabolism; D005343:Fibrinolytic Agents; D006801:Humans; D010726:Phosphodiesterase Inhibitors; D010974:Platelet Aggregation / Q000187:drug effects; D013928:Thromboxane A2 / Q000096:biosynthesis
D005343:Fibrinolytic Agents; D010726:Phosphodiesterase Inhibitors; D013928:Thromboxane A2; D004176:Dipyridamole; D005340:Fibrinogen; D011464:Epoprostenol; D000241:Adenosine