The in vitro and ex vivo antiplatelet effect of TRK-100, a stable prostacyclin analog, in several species.
Effect of TRK-100, a stable PGI2 analog, on platelet function was tested in vitro and ex vivo. TRK-100 at the dose range of 0.5-300 nM inhibited platelet aggregation induced by arachidonic acid, adenosine 5'-diphosphate and collagen in several species including human platelets. The potency of TRK-100 was 1/2 to 1/5 that of PGI2. The effect was strong in human and cat platelets. In conscious rabbits and rats, oral TRK-100 at the dose range of 0.1-1 mg/kg inhibited ex vivo platelet aggregation up to 80% in the rat and 70% in the rabbit, and the effect lasted over 5 hr. However, in both species, the effect on blood pressure was minimal. In anesthetized rabbits, inhibition of platelet aggregation was the same level as in the conscious animal, but blood pressure depression was observed. Cyclic AMP levels of human platelets, 2 min after incubation, was elevated up to 2.4 microM/10(9) platelets by 100 ng/ml of PGI2 and 1.5 microM by 100 ng/ml of TRK-100. It was shown that TRK-100 has a potent antiplatelet effect both in vitro and ex vivo in many species through elevation of platelet cAMP. These results suggest that TRK-100 may be a potential oral antithrombotic drug.
Nishio
S
S
Toray Industries, Inc., Basic Research Laboratories, Kamakura, Japan.
Matsuura
H
H
Kanai
N
N
Fukatsu
Y
Y
Hirano
T
T
Nishikawa
N
N
Kameoka
K
K
Umetsu
T
T
D000244:Adenosine Diphosphate / Q000097:blood; D000527:Alprostadil / Q000097:blood; D000818:Animals; D002415:Cats; D000242:Cyclic AMP / Q000097:blood; D004285:Dogs; D011464:Epoprostenol / Q000097:blood / Q000494:pharmacology* / Q000031:analogs & derivatives; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D013045:Species Specificity
D010975:Platelet Aggregation Inhibitors; C048081:beraprost; D000244:Adenosine Diphosphate; D011464:Epoprostenol; D000242:Cyclic AMP; D000527:Alprostadil