A comparison of the effects of three positive inotropic agents (amrinone, milrinone and medorinone) on platelet aggregation in human whole blood.
Amrinone, milrinone and medorinone inhibit platelet aggregation in human whole blood. They are particularly potent inhibitors of arachidonic acid induced aggregation, inhibiting by 50% (IC50) at concentrations of 1.5 microM (milrinone), 7.5 microM (medorinone) and 48 microM (amrinone). Each drug was less potent at inhibiting ADP and collagen-induced aggregation. The rank order for inhibition of arachidonic acid - induced aggregation correlated well with the rank order of cyclic AMP phosphodiesterase inhibition for these drugs when compared to the response of a reference cAMP phosphodiesterase inhibitor (CI-930) and a reference cGMP phosphodiesterase inhibitor (M & B 22948). Since inhibition of platelet aggregation in vitro occurred at clinically relevant concentrations, it is evident that these agents have potentially beneficial antithrombotic properties.
Pattison
A
A
Sterling Winthrop Research Centre, Alnwick, Northumberland, United Kingdom.
Astley
N
N
Eason
C T
CT
Bonner
F W
FW
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000638:Amiodarone / Q000494:pharmacology*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003094:Collagen / Q000494:pharmacology; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006801:Humans; D008297:Male; D020105:Milrinone; D009287:Naphthyridines / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011724:Pyridazines / Q000494:pharmacology; D011728:Pyridones / Q000494:pharmacology*
D001095:Arachidonic Acids; D002316:Cardiotonic Agents; D005343:Fibrinolytic Agents; D009287:Naphthyridines; D010975:Platelet Aggregation Inhibitors; D011724:Pyridazines; D011728:Pyridones; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; C064867:medorinone; C042528:4,5-dihydro-6-(4-(imidazol-1-yl)phenyl)-5-methyl-3(2H)-pyridazinone; D003094:Collagen; D020105:Milrinone; D000638:Amiodarone