Beraprost

Details:

This orally active epoprostenol analogue (FW = 398.50 g/mol; CAS 88475- 69-8; Soluble to 25 mM in DMSO), also named TRA-418 and 2,3,3a,8b- tetrahydro-2-hydroxy-1- (3-hydroxy-4-methyl-1-octen-6-yn-1-yl) -1H- cyclopenta[b]benzofuran-5-butanoic acid, is a potent agonist for the Prostacyclin Receptor, a member of the G-protein coupled receptor family. Prostacyclin, the major product of cyclooxygenase in macrovascular endothelium, elicits a potent vasodilation and inhibition of platelet aggregation through binding to this receptor. Beraprost potently inhibits ADP-induced platelet aggregation (pIC50 = 8.26) and P-selectin expression in vitro (pIC50 = 8.56). It also increases vasodilation and reduces pulmonary hypertension in vivo. TRA-418 inhibited platelet GPIIb/IIIa activation as well as induction of P-selectin expression by adenosine 5'-diphosphate, Thrombin Receptor Agonist Peptide 1-6 (Ser-Phe-Leu-Leu-Arg-Asn-NH2), and U-46619 in the presence of epinephrine. TRA-418 also inhibits platelet aggregation induced by those platelet-stimulants in Ca2+-chelating anticoagulant, citrate and in nonchelating anticoagulant, d-phenylalanyl-l- prolyl-l-arginyl-chloromethyl ketone (PPACK). The TP-receptor antagonist SQ-29548 inhibited only U-46619+epinephrine-induced GPIIb/IIIa activation, P-selectin expression, and platelet aggregation. The IP-receptor agonist beraprost sodium inhibited platelet activation. Beraprost also inhibited platelet aggregation induced by platelet stimulants we tested in citrate and in PPACK. The GPIIb/IIIa inhibitor abciximab blocked GPIIb/IIIa activation and platelet aggregation. However, abciximab showed slight inhibitory effects on P-selectin expression. TRA-418 is more advantageous as an antiplatelet agent than TP-receptor antagonists or IP- receptor agonists separately used.