Effect of a stable prostacyclin analogue on platelet function and experimentally-induced thrombosis in the microcirculation

Arzneimittelforschung. 1985;35(12):1816-8.


Sodium dl-4-[1R,2R,3aS,8bS)-1,2,3a,8b-tetrahydro- 2-hydroxy-1-[(3S,4RS)-3-hydroxy-4-methyl-oct-6- yne-(E)-1-enyl]-5-cyclopenta[b]benzofuranyl]butyrate (TRK-100) is a stable analogue of prostacyclin (epoprostenol, PGI2). The drug was shown to be a potent inhibitor of platelet aggregation in vitro, induced by adenosine diphosphate (ADP), using platelet-rich plasma (PRP) from human and several animal species. The inhibitory activity of TRK-100 using human platelets was half that of PGI2 and eight times that of PGE1. There was a marked tendency for platelet clumps to disaggregate following secondary aggregation in the presence of TRK-100 at final concentrations higher than 1 ng/ml. This activity was similar to PGI2 and more than 30 times that of PGE1. TRK-100 was shown to induce the disaggregation of a pre-existing thrombus in the microcirculation of the hamster cheek pouch. A dose-dependent response was obtained following oral administration of the drug at levels of 50-200 micrograms/kg. Optimal activity was observed 30-60 min after dosing and activity was sustained throughout the experimental period. TRK-100 was more active than PGE1 in the test system and appeared to be of a similar potency to PGI2. Since this drug is stable, orally active and without the hypotensive activity of PGI2, it is considered to be a potentially useful agent for antithrombotic therapy.

MeSH terms

  • Adenosine Diphosphate / antagonists & inhibitors
  • Adenosine Diphosphate / pharmacology
  • Alprostadil / pharmacology
  • Animals
  • Cricetinae
  • Dogs
  • Epoprostenol / pharmacology*
  • Fibrinolytic Agents*
  • Guinea Pigs
  • Humans
  • In Vitro Techniques
  • Male
  • Mesocricetus
  • Microcirculation / drug effects*
  • Platelet Aggregation / drug effects*
  • Rabbits
  • Rats
  • Species Specificity
  • Time Factors


  • Fibrinolytic Agents
  • beraprost
  • Adenosine Diphosphate
  • Epoprostenol
  • Alprostadil