The effect of 5-(2-chlorobenzyl)-5,6,7,7a-tetrahydro 4H-thieno (3.2-C)-pyridine-2-one hydrochloride (PCR 3787), a metabolite of ticlopidine, on the aggregation of human platelets in vitro and on the aggregation inhibiting action of PGI2 and PGD2.
A metabolite of ticlopidine, PCR 3787, in concentrations from 25-200 micrograms/ml inhibited the aggregation of human platelets, induced by different amounts of collagen. The effect of PCR 3787 on PG formation was tested in rat platelets. After incubation with PCR 3787, platelets were labelled with 1-14C arachidonic acid and aggregation induced with collagen. The sum of the PG formed (PGF2 alpha + PGE2 + PGD2) was higher in the platelets incubated with PCR 3787 than in the controls. The aggregation-inhibiting effects of PGI2 (1 ng/ml) and PGD2 (10 ng/ml) on human platelets were enhanced by the addition of PCR 3787 (100 micrograms/ml). A stable derivative of PGI2, ciloprost was used. These results indicate, that part of the aggregation-inhibiting effect of ticlopidine can be attributed to the formation of this metabolite.
D003094:Collagen / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology*; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects*; D015230:Prostaglandin D2; D011457:Prostaglandins D / Q000494:pharmacology*; D013876:Thiophenes / Q000378:metabolism / Q000494:pharmacology*; D013988:Ticlopidine / Q000031:analogs & derivatives
D011457:Prostaglandins D; D013876:Thiophenes; D003094:Collagen; C044715:PCR 3787; D011464:Epoprostenol; D013988:Ticlopidine; D015230:Prostaglandin D2