Effect of beraprost sodium on peripheral circulation insufficiency in rats and rabbits.
Beraprost sodium (sodium (+/-)-(1R*,2R*,3aS*,8bS*)-2,3,3a,8b-tetrahydro-2- hydroxy-1-[(E)-(3S*)-3-hydroxy-4-methyl-1-octen-6-ynyl]-1H- cyclopenta[b]benzofuran-5-butyrate, TRK-100) is a chemically and biologically stable epoprostenol analogue which possesses both potent antiplatelet and peripheral vasodilating actions. Its effect on obstruction of the peripheral artery was studied in three different models: 1. acute thrombosis induced by electrical-stimulation of the femoral artery in rabbits, 2. occlusion induced by intra-arterial injection of sodium laurate in rats and 3. tail gangrene induced by subcutaneous injections of both ergotamine and epinephrine in rats. Oral administration of beraprost sodium resulted in suppression of thrombus formation in the acute thrombosis model, marked improvement of macroscopic and histological observations in the laurate-occlusion model and inhibition of tail gangrene extension. In contrast, ticlopidine improved thrombus formation in the acute thrombosis model and slightly improved histological observation in the laurate-occlusion model, but not in the tail gangrene model. Cilostazol suppressed lesions in the acute thrombosis model, but not in the tail gangrene model. These findings suggest that beraprost sodium may be very useful clinically for the therapy of peripheral circulation insufficiency diseases such as Buerger's disease and Raynaud's disease.
Murai
T
T
Pharmacological Laboratory, Kaken Pharmaceutical Co., Ltd., Tokyo, Japan.
Muraoka
K
K
Saga
K
K
Sakai
A
A
Sato
N
N
Amemiya
K
K
Yajima
M
M
Murata
T
T
Umetsu
T
T
Nishio
S
S
D000208:Acute Disease; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D004558:Electric Stimulation; D004837:Epinephrine / Q000494:pharmacology; D011464:Epoprostenol / Q000627:therapeutic use* / Q000031:analogs & derivatives; D004878:Ergotamine / Q000494:pharmacology; D005260:Female; D005734:Gangrene; D007850:Lauric Acids / Q000494:pharmacology; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects*; D013623:Tail / Q000098:blood supply / Q000473:pathology; D013927:Thrombosis / Q000188:drug therapy
D007850:Lauric Acids; D010975:Platelet Aggregation Inhibitors; C030358:lauric acid; C048081:beraprost; D011464:Epoprostenol; D004878:Ergotamine; D004837:Epinephrine