Protective effect of RS-5186 against endotoxin-induced disseminated intravascular coagulation (DIC) in rats

• Published in: Japanese Journal of Pharmacology 1989, Vol.49 (suppl), p.321-321
• Main Authors: Kawachimaru, Naoaki, Yazawa, Naoko, Ito, Tomiyoshi, Nagasawa, Takako, Asai, Fumitoshi, Oshima, Takeshi
• Format: Article
• Language: English
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)56798-1

We have previously reported that RS-5186 is a potent and highly selective thromboxane (TX) A2 synthetase inhibitor (Thromb. Res., 51, 507-520, 1988). The present study was designed to evaluate the effect of RS-5186 on experimental DIC induced by endotoxin in anesthetized rats. RS-5186 (0.3, 3 and 30 mg/kg) was orally administered 1 hr before the start of 4 hr sustained intravenous infusion of endotoxin (E. coli, lipopolysaccharide 055：B5, Difco) at a dose of 25 mg/kg. As a result, preventive effects against DIC were significantly noted in rats treated with 3 and 30 mg/kg RS-5186 in all the parameters：activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), platelet count, fibrinogen level (Fbg), fibrinogen/fibrin degradation products (FDP) and the number of renal glomeruli with fibrin deposit (%GFD). The inhibition of the increase in the plasma TXB2 level was also observed in the treatment with RS-5186. These results suggest that RS-5186 may be useful for the treatment of DIC.