Beraprost C??? ??, ??, ??
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Platelet aggregation inhibitor; stable analog of Prostacyclin. Antithrombotic; vasodilator (peripheral).
Mechanism of action
Beraprost is a chemically stable, oral form of prostacyclin that is readily absorbed from GI
tract. Like natural prostacyclin, beraprost dilates blood vessels, prevents platelet aggregation, and prevents
proliferation of smooth muscle cells surrounding blood vessels. It may be an important treatment for early stage PVD
and for early stage pulmonary hypertension. Intermittent oral doses of beraprost, however, do not seem to provide the
consistent blood levels
necessary to treat the advanced stages of pulmonary hypertension.
Clinical Use
Beraprost is an oral formulation of a prostacyclin analog for the treatment of early stage pulmonary hypertension as
well as early stage PVD.
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Adverse
effects include headache, flushing, jaw pain, and diarrhea.
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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. TRA-418 showed a different inhibitory
profile from abciximab in the effects on P-selectin expression.
Beraprost ?? ?? ? ???
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