Anticoagulant activity of the novel thrombin inhibitor 1-butyl-3-(6,7-dimethoxy-2-naphthylsulfonyl) amino-3-(3-guanidinopropyl)-2-pyrrolidinone hydrochloride.

1 Butyl-3-(6,7-dimethoxy-2-naphthylsulfonyl)amino-3-(3-guanidinopropyl 1-2-pyrrolidinone hydrochloride (CAS 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 IC 50 of SPI-501 was 1.7 μmol/I. Argipidine also prolonged coagulation time and its activity was one order of magnitude greater than that of SPI-501. SPI-501 and argipidine caused dose-dependent increases in the activated partial prothrombin time (APTT) and prothrombin time (PT) of rat plasma. When APTT and PT were measured, IC 50 values of SPI-501 were 38.0 and 18.5 μmol/I and those of argipidine, 1.4 and 1.9 μmol/I, respectively. Intravenous administration of SPI-501 (10 and 30 μmol/kg) and argipidine (I and 3 μmol/kg) prolonged both APTT and PT in rats. While SPI-501 was less potent than argipidine, the durations of the effects of both were the same.