The pharmacological characteristics of the 3-oxamethano-prostaglandin I1 compound (+)-methyl [2-[(2R,3aS,4R,5R,6aS)-octahydro-5-hydroxy-4- [(E)-(3S,5S)-3-hydroxy-5-methyl-1-nonenyl]-2-pentalenyl]etho xy]
acetate (SM-10902, CAS 139403-31-9), a novel stable analogue of
prostacyclin and its free
acid,
SM-10906, were studied.
SM-10902 was rapidly deesterified to its free
acid in rabbit and human serum.
SM-10902 and
SM-10906 exhibited antiplatelet potency against
ADP-induced aggregation in rabbit and human platelets. In the presence of diisopropyl
fluorophosphate, an
esterase inhibitor, the antiplatelet activity of
SM-10902 was markedly reduced, to much less than that of
SM-10906.
SM-10906 inhibited platelet aggregation induced by various inducers in several species and enhanced the
cyclic AMP (cAMP) level in human platelets. These activities were nearly equal to those of
prostaglandin (PG) E1 and less than those of PGI2.
SM-10906 relaxed isolated rabbit mesenteric and bovine coronary arteries, and elevated the cAMP level in bovine coronary arteries.
SM-10906 given intravenously exhibited a sustained reduction in blood pressure based on vasodilation in
ganglion-blocked,
angiotensin II-supported rats.
SM-10902 applied to the guinea-pig auricles increased the skin temperature, but
SM-10906 and PGI2 showed no such effect. In conclusion,
SM-10902, which is considered to be a
prodrug of
SM-10906, was suggested to exert its anti-platelet and
vasodilator activities through the increase of cAMP. Since
SM-10902 penetrates well into the skin, it may be useful as an external preparation to improve peripheral circulatory insufficiency.