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-guanidin opropyl)-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 IC50 of SPI-501 was 1.7 mumol/l. 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, IC50 values of SPI-501 were 38.0 and 18.5 mumol/l and those of argipidine, 1.4 and 1.9 mumol/l, respectively. Intravenous administration of SPI-501 (10 and 30 mumol/kg) and argipidine (1 and 3 mumol/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.
Okayama
T
T
Research Institute, Fuji Chemical Industries, Co., Ltd., Toyaman, Japan.
Araki
S
S
Miyamae
T
T
Morita
Y
Y
Morikawa
T
T
Hagiwara
M
M
D000818:Animals; D000925:Anticoagulants / Q000138:chemical synthesis* / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D010314:Partial Thromboplastin Time; D011517:Prothrombin Time; D011760:Pyrrolidinones / Q000138:chemical synthesis* / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013917:Thrombin / Q000037:antagonists & inhibitors*
D000925:Anticoagulants; D006146:Guanidines; D011760:Pyrrolidinones; C109120:SPI 501; D013917:Thrombin