op-41483-alpha-cyclodextrin and Thrombocytopenia

The effects of OP-41483.alpha-CD, 5(E)-6,9-deoxa-6,9 alpha-methylene-15-cyclopentyl-16,17,18,19,20-pentanor prostacyclin (PGI2).alpha-cyclodextrin clathrate, on platelet function and experimental thrombosis were studied. In human platelets, OP-41483 inhibited aggregation induced by adenosine diphosphate (ADP) or collagen, promoted disaggregation, and elevated cyclic adenosine monophosphate (cAMP) levels in vitro at the same order of concentrations. The equipotent antiaggregatory activity of OP-41483 to human platelets was observed in monkey platelets in vitro. Furthermore, intravenous administration of OP-41483 to monkeys, unlike PGI2, showed the antiaggregatory effect on platelets but with less effect on blood pressure, suggesting that a differential sensitivity to OP-41483 between platelet function and vascular tone exists in monkeys. In rabbits, OP-41483.alpha-CD attenuated platelet aggregation induced by ADP, collagen and platelet activating factor (PAF), decreased circulating platelet aggregates, and inhibited platelet adhesiveness to de-endothelialized blood vessels. These results suggest that the anti-thrombotic effects of OP-41483 are associated with its potent antiplatelet activities mainly because of the elevation of cAMP levels in the platelets. The potent anti-thrombotic and less hypotensive effects of this compound may be useful for various thrombotic disorders.

Topics: Adenosine Diphosphate; alpha-Cyclodextrins; Animals; Arachidonic Acid; Blood Coagulation Factors; Blood Platelets; Blood Pressure; Collagen; Cyclodextrins; Dogs; Epoprostenol; Female; Fibrinolytic Agents; Humans; Macaca; Male; Platelet Activating Factor; Platelet Adhesiveness; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Count; Rabbits; Rats; Rats, Wistar; Species Specificity; Thrombocytopenia