ANTIPLATETLET AND ANTITHROMBOTIC EFFECTS OF OP-41483-CENTER-DOT-ALPHA-CD, A PROSTACYCLIN ANALOG, IN EXPERIMENTAL-ANIMALS

The effects of OP-41483.alpha-CD, 5(E)-6,9-deoxa-6,9 a-methylene-15-cy clopentyl-16,17,18,19,20-pentanor prostacyclin (PGI2).alpha-cyclodextr in clathrate, on platelet function and experimental thrombosis were st udied. In human platelets, OP-41483 inhibited aggregation induced by a denosine diphosphate (ADP) or collagen, promoted disaggregation, and e levated cyclic adenosine monophosphate (cAMP) levels in vitro at the s ame order of concentrations. The equipotent antiaggregatory activity o f OP-41483 to human platelets was observed in monkey platelets in vitr o. Furthermore, intravenous administration of OP-41483 to monkeys, unl ike 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 monk eys. In rabbits, OP-41483-alpha-CD attenuated platelet aggregation ind uced by ADP, collagen and platelet activating factor (PAF), decreased circulating platelet aggregates, and inhibited platelet adhesiveness t o de-endothlialized blood vessels. These results suggest that the anti -thrombotic effects of OP-41483 are associated with its potent antipla telet 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.