title: Anti-platelet effects of isocarbacyclin methyl ester on human and rabbit platelets in vitro.
abstract: Anti-platelet effects of isocarbacyclin methyl ester (CAS 88931-51-5, TEI-9090) and of its free acid form, TEI-7165 (CAS 88911-35-7) were compared with those of prostaglandin (PG) I2 and PGE1. TEI-9090 and TEI-7165 dose-dependently inhibited human and rabbit platelet aggregation and human platelet adhesion in vitro. The IC50 values of TEI-9090, TEI-7165, PGI2, and PGE1 against ADP-induced human (rabbit) platelet aggregation were 22.90 (25.00) ng/ml, 2.78 (6.46) ng/ml, 1.67 (3.34) ng/ml, and 19.91 (8.32) ng/ml, respectively; and those against human platelet adhesion were 3.47 ng/ml, 0.13 ng/ml, 0.25 ng/ml, and 1.45 ng/ml, respectively. TTC-909, a product incorporating TEI-9090 in lipid microspheres, had an aggregation inhibitory effect similar to that of TEI-9090 in human platelets. The aggregation inhibitory effect of TEI-9090 and TTC-909 increased with incubation time, and reached a level similar to that of TEI-7165. In contrast, the aggregation inhibitory effect of TEI-7165 remained constant for 120 min, whereas that of PGI2 decreased with time. TEI-9090 and TEI-7165 also enhanced the disaggregation of human platelets at nearly the same concentration as they exerted their inhibitory effect on aggregation. The order of anti-platelet activities, compared at each optimum incubation point, were PGI2 approximately equal to TEI-7165 approximately equal to TEI-9090 (approximately equal to TTC-909) > PGE1 in human and rabbit platelets. These results indicate that TEI-9090 (TTC-909) and its active metabolite, TEI-7165, may be a potent anti-platelet drug.
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000187:drug effects*; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits
chemical_list: D010975:Platelet Aggregation Inhibitors; C052840:TEI 9090; C041946:9-O-methanoprostaglandin I; D011464:Epoprostenol