Inhibitory Effect of OP-41483・α-CD, a Prostacyclin Analog, on Peripheral Vascular Lesion Models in Rats

• Published in: Japanese Journal of Pharmacology 1992, Vol.59 (1), p.57-63
• Main Authors: Korekiyo Wakitani, Toshio Takakuwa, Makiko Sugioka, Buichi Fujitani, Hideki Aishita
• Format: Article
• Language: Japanese
• ISSN: 0021-5198

The effect of a chemically stable prostacyclin analog, OP-41483 α-cyclodextrin clathrate (OP-41483・α-CD), on vascular lesions, platelet aggregation and blood pressure were examined and compared with those of prostaglandin E_1 α-cyclodextrin clathrate (PGE_1 ・CD) in in vivo rat models. 1) In the laurate (1 mg/leg, i.a.)-induced arterial thrombotic model, OP-41483・α-CD (1 μg/kg/min, i.v.) prevented the progression of femoral arterial vascular lesions and enhanced the development of collaterals in the femoral artery. PGE_1 ・CD did not inhibit the progression of vascular damages. 2) In the model of vasoconstriction induced by epinephrine (0.05 mg/tail, s.c.) and ergotamine (2 mg/kg, s.c.), OP-41483・α-CD and PGE_1 ・CD, at 1 μg/kg/min, inhibited the progress of tail gangrene and lessened the decrease in tail cutaneous blood flow. 3) OP-41483・α-CD (1 μg/kg/min) suppressed the ADP (0.1 mg/kg/min, i.v.)-induced decrease in the number of circulating platelets without affecting the change in blood pressure. In contrast, PGE_1 ・CD (3μg/kg/min) inhibited ADP-induced thrombocytopenia with a decrease in blood pressure. These results indicate that OP-41483・α-CD has antiplatelet and cutaneous blood flow improving activities that are greater than its hypotensive effect and may be of therapeutic potential in peripheral vascular diseases.