The effects of amrinone on human platelet aggregation: evidence that amrinone does not act through a cyclic nucleotide mechanism in platelet rich plasma.
The purpose of the present study was to investigate in human platelet rich plasma the effects of amrinone, a cardiotonic agent, on platelet aggregation induced by ADP, arachidonic acid (AA), collagen, prostaglandin H2 (PGH2), and U46619, a substance reported to mimic the actions of thromboxane A2. Amrinone inhibited aggregatory responses to all substances studied in a dose-related fashion and this is the first report demonstrating the inhibitory actions of amrinone on platelet aggregation induced by PGH2. Although amrinone inhibited aggregatory responses to ADP, collagen, PGH2, and U46619 at similar doses, markedly lower doses of amrinone were necessary to inhibit aggregatory responses to AA. Furthermore, amrinone did not alter cAMP and cGMP levels in human platelet rich plasma. The present data demonstrate that amrinone inhibits human platelet aggregation induced by a variety of substances and independent of changes in cAMP and cGMP levels. Furthermore, the present data suggest that amrinone selectively inhibits aggregatory responses to arachidonic acid prior to the formation of thromboxane A2.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000631:Aminopyridines / Q000494:pharmacology*; D000676:Amrinone; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D003094:Collagen / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009712:Nucleotides, Cyclic / Q000097:blood*; D010974:Platelet Aggregation / Q000187:drug effects*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D044262:Prostaglandin H2; D011463:Prostaglandins H / Q000494:pharmacology
D000631:Aminopyridines; D001095:Arachidonic Acids; D009712:Nucleotides, Cyclic; D011450:Prostaglandin Endoperoxides, Synthetic; D011463:Prostaglandins H; D016718:Arachidonic Acid; D044262:Prostaglandin H2; D000244:Adenosine Diphosphate; D003094:Collagen; D000676:Amrinone