ANTICOAGULANT ACTIVITY OF THE NOVEL THROMBIN INHIBITOR LFONYL)AMINO-3-(3-GUANIDINOPROPYL)-2-PYRROLIDINONE HYDROCHLORIDE

lfonyl)amino-3-(3-guanidinopropyl)-2-pyrrolidinone hydrochloride (GAS 173440-64-7, SPI-501), which has highly selective thrombin-inhibitory activity, caused a concentration-dependent increase in the time taken for coagulation induced by thrombin in rabbit plasma. The IC50 of SPI- 501 was 1.7 mu mol/l. Argipidine also prolonged coagulation time and i ts activity was one order of magnitude greater than that of SPI-501. S PI-501 and argipidine caused dose-dependent increases in the activated partial prothrombin time (APTT) and prothrombin time (PT) of rat plas ma. When APTT and PT were measured, IC50 values of SPI-501 were 38.0 a nd 18.5 mu mol/l and those of argipidine, 1.4 and 1.9 mu mol/l, respec tively. Intravenous administration of SPI-501 (10 and 30 mu mol/kg) an d argipidine (1 and 3 mu mol/kg) prolonged both APTT and PT in rats. W hile SPI-501 was less potent than argipidine, the durations of the eff ects of both were the same.