NEW PENTAMIDINE RELATED SUBSTANCES WHICH SIMULTANEOUSLY INHIBIT PLATELET-AGGREGATION AND ACCELERATE PLASMIN GENERATION AND IN-VITRO CLOT LYSIS

Pentamidine, a highly toxic drug, possesses RGD-peptide (Arg-Gly-Asp)- like antiplatelet actions. The objective of this investigation was to study the anticipated profibrinolytic and antiplatelet actions of pent amidine and of pentamidine (bearing guanidino-like groups)-related syn thetic peptidomimetic compounds. platelet aggregation inhibition was a ssessed using ADP, thrombin, collagen, arachidonic acid and epinephrin e as inducers, by aggregometry, In vitro chromogenic plasmin generatio n tests and clot lysis assays were also performed Two (assigned as D-2 and D-3) of the synthetic pentamidine-guanidino related molecules wer e able to inhibit platelet aggregation and simultaneously accelerate i n vitro plasmin generation and dot-lysis in the nM range. These dual a ction antithrombotic agents now need to be tested further to assess th eir antithrombotic actions in vivo.