ONO-1301 [(E)-[5-[2-[1-phenyl-1-(3-pyridyl)methylidene-aminooxy]ethyl]-7,8-dihydronaphthalene-1-yloxy]acetic acid] is a novel prostaglandin (PG) I2 mimetic with inhibitory activity on thromboxane (TX) A2 synthase. ONO-1301 retains its inhibitory effect on platelet aggregation after repeated administration, while beraprost, a representative PGI2 agonist, loses its inhibitory effect after repeated administration. In addition, ONO-1301 inhibited arachidonic acid–induced TXA2 production in platelets lacking PGI2 receptor (IP). Beraprost could retain its antiplatelet effect after repeated administration in combination if it was dosed with ozagrel, a TXA2 synthase inhibitor. Therefore, it was hypothesized that chronic IP stimulation by beraprost induces an increase in TXA2 production, leading to reduction in the antiplatelet effect. As expected, repeated administration of beraprost increased the plasma and urinary levels of a TXA2 metabolite, while ONO-1301 did not. In addition, beraprost could retain the ability to inhibit platelet aggregation after repeated administration in mice lacking the TXA2 receptor TP.
See article at J Pharmacol Exp Ther 2015, 353:269–278.
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