Key result
OP-1206 dose-dependently inhibited thrombus formation without affecting PGI2 synthesis, whereas the antithrombotic effect of acetylsalicylic acid was lessened at high doses due to PGI2 inhibition.
Why the study?
Does OP-1206 improve antithrombotic effects compared to acetylsalicylic acid in a guinea-pig thrombosis model?
Does OP-1206 improve antithrombotic effects compared to acetylsalicylic acid in a guinea-pig thrombosis model?
Answers are grounded in this paper and cite their sources.
OP-1206 demonstrates a more complete antithrombotic effect than high-dose acetylsalicylic acid in a guinea-pig thrombosis model, as the efficacy of acetylsalicylic acid is limited by its inhibition of endogenous PGI2 formation.
The antithrombotic effect of a prostaglandin E1 derivative, OP-1206 (17S-20-dimethyl-trans-Δ2-PGE1)⋅α-cyclodextrin clathrate (OP-1206⋅α-CD), was compared with that of acetylsalicylic acid (ASA) in a electrically induced thrombosis model of guinea-pig mesenteric arteries using intact animals and animals subjected to the superfusion of tranylcypromine (TC, 15 mM) over their mesentery. The drug-effect was assessed by the change of the threshold voltage for the thrombus formation. 1) TC (1.5–15 mM) lowered the threshold voltage, and the effect was comparable to its inhibitory effect on PGI2 formation in vitro, investing that PGI2 generated in mesenteric arteries acts to prevent thrombus formation. 2) In intact animals, OP-1206⋅α-CD at doses of 0.01–0.3 mg/kg, p.o. (as OP-1206), significantly and dose-dependently elevated the threshold voltage. ASA 30–1000 mg/kg, p.o.) significantly elevated the threshold voltage, but the effect reached to its maximum at 100 mg/kg and lessened with further Increase of 3) In TC-treated animals, OP-1206⋅α-CD elevated the threshold voltage dose-dependently, but the elevation of threshold voltage by ASA reached to its plateau evel which was significantly lower than that obtained with OP-1206⋅α-CD at 0.3 mg/kg, indicating that the antithrombotic effect of ASA is incomplete in this model. 4) Threshold voltages in TC-treated animals given OP-1206⋅α-CD was significantly lower than those in intact animals at all doses tested, but threshold voltages in TC-treated and intact animals given ASA at 300–1000 mg/kg were not different, suggesting that high doses of ASA inhibits PGI2 formation in vivo. Thus, the antithrombotic effect of ASA was restricted by its inhibitory effect on PGI2 formation and its incomplete inhibition on thrombus formation, while such differences were not observed in OP-1206⋅α-CD.
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Fujitani et al. (1986) studied Electrically induced thrombosis. OP-1206 and Acetylsalicylic acid vs. Control (intact and tranylcypromine-treated) was evaluated on Threshold voltage for thrombus formation. OP-1206 dose-dependently inhibited thrombus formation without affecting PGI2 synthesis, whereas the antithrombotic effect of acetylsalicylic acid was lessened at high doses due to PGI2 inhibition.
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