Antithrombotic effect of topically applied 3-oxa-methano-prostaglandin I1 in the microcirculation and antiplatelet functions of its active form.
The antithrombotic effect of topical application of the 3-oxa-methano-prostaglandin (PG) I1 analog, SM-10902 in the microcirculation and in vitro antiplatelet functions of its active form SM-10906 were estimated in comparison with PGI2 and PGE1. In rat platelets, SM-10906 evoked accumulation of intracellular cyclic adenosine 3',5'-monophosphate, and exhibited antiaggregatory and disaggregatory activities, which were all enhanced by the phosphodiesterase inhibitor theophylline. Additionally, SM-10906 was shown to inhibit platelet adhesion to collagen in human platelet-rich plasma. PGI2 and PGE1 also showed in vitro antiplatelet effects in the order of PGI2 > SM-10906 > or = PGE1. SM-10902 exhibited a dose-dependent anti-thrombotic effect in the guinea pig mesenteric arteriole by a topical application, and this activity might be exerted by the antiplatelet functions of SM-10906. Although SM-10906, PGI2 and PGE1 also showed the antithrombotic effects, SM-10902 was the most potent. In conclusion, the present studies indicate that an external topical preparation of SM-10902 may be useful for the therapy of peripheral circulatory insufficiency.
Nishimura
T
T
Research Center, Sumitomo Pharmaceuticals Co., Osaka, Japan.
Yamamoto
S
S
Yamamoto
T
T
Kaneko
M
M
Hara
Y
Y
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D000287:Administration, Topical; D000818:Animals; D000242:Cyclic AMP / Q000097:blood; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D015394:Molecular Structure; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D051381:Rats; D013927:Thrombosis / Q000188:drug therapy*
D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; C086699:SM 10906; C086698:SM 10902; D011464:Epoprostenol; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases