In vitro studies with the stabilized epoprostenol analogue taprostene. Effect on platelets and erythrocytes.
In vitro, the oxacyclic epoprostenol (prostacyclin) analogue taprostene like the native epoprostenol inhibited platelet aggregation and adhesion and induced deaggregation. Antiaggregatory action of taprostene was demonstrated towards arachidonic acid-, ADP-, thrombin- and norepinephrine-induced aggregations of human platelet rich plasma with IC50 values between 17 and 34 nmol/l. ADP-induced aggregations of human, dog or rabbit platelets were inhibited with an equivalent efficacy. Under the present conditions taprostene was about 3fold less active than epoprostenol. The deaggregatory effect, measured in arachidonic acid-induced aggregates of human PRP, could be detected only in concentrations from 1 mumol/l taprostene. The adhesion-inhibiting effect towards glass beads, measured in whole blood, appeared at comparable high concentrations (IC50 value: 2.4 mumol/l) and likewise the antihaemolytic effect on rat erythrocytes, which was exerted with a threshold concentration of 10 mumol/l. Heparin in a concentration range of 0.1-1000 micrograms/ml increased thrombocyte adhesion and this effect was prevented by 1 mumol/l taprostene.
Michel
G
G
Department of Pharmacology, Grünenthal GmbH, Aachen, Fed. Rep. of Germany.
Seipp
U
U
D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects*; D004285:Dogs; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004910:Erythrocyte Membrane / Q000187:drug effects*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D013045:Species Specificity
D010975:Platelet Aggregation Inhibitors; C022228:5,6-dihydroprostacyclin; C039188:taprostene; D011464:Epoprostenol; D000527:Alprostadil