Studies on the inhibitory effects of heparin, hirudin or OM-189 (synthetic thrombin inhibitor by Okamoto) on the Serine proteases (thrombin, trypsin, Factor Xa and plasmin) by the method using synthetic chromogenic substrate

Abstract

The inhibitory effects of heparin, hirudin and OM-189 (Okamoto's synthetic thrombin inhibitor) on serine proteases were investigated by the estimating method using synthetic chromogenic substrate, and the results were as follows:
(1) When heparin was added to plasma, antithrombin activity was increased, but decreased with addition of protamin sulfate.
(2) Hirudin showed remarkable inhibitory effects on the proteolytic activity of trypsin and thrombin, and when hirudin (0.2mg) was infused into a rabbit (2.5kg by weight) PTT and thrombin time were prolonged with no changes of plateletes and fibrinogen.
(3) OM-189 showed the inhibitory effects on the ploteolytic activities of trypsin, thrombin, Factor Xa and plasmin remarkably. When OM-189 (4.8mg) was injected into a rabbit, inhibitory effects similer to the results found in the case of hirudin were observed. The inhibitory effect of OM-189 to the activity of Defibrase was observed in the concentration of 1mol of it, but was not observed by the estimating method using fibrinogen as the substrate.