In vivo profile of the anticoagulant effect of 17ß-amino-1,3,5(10)estratrien-3-ol

The anticoagulant activity of 17ß-amino-1,3,5(10)estratrien-3-ol (AE2) was established for the first time. Experiment 1: mice groups were treated with a single subcutaneous (s.c.) AE2 injection (0.5, 1, 2, 4, and 8 mg/100 g BW) or vehicle (propylenglycol; 0.5 ml/100 g). After 24 h, AE2 produced dose-dependent blood clotting time increases related to control, Emax=+121% (P<0.01) finishing the sixth day. Experiment 2: four groups received a single s.c. administration of AE2 (4 or 8 mg/100 g BW) or 17ß-estradiol (E2; 3 mg/100 g BW) or vehicle. After 24 and 48 h post-administration, the times of blood clotting, prothrombin, thrombin, and activated partial thromboplastin and fibrinogen concentrations were assessed. Both AE2 doses increased blood clotting and fibrinogen similarly, blood clotting time: 64, 94%; fibrinogen: 71, 107% (P<0.01). Prothrombin, activated partial thromboplastin and thrombin times, increased 13-15%, 27-55%, and 15-29%, respectively (P<0.01). Meanwhile E2 decreased blood clotting 20% (P<0.01) and thrombin 23% (P<0.01) after 48 h. Experiment 3: for five consecutive days, mice received AE2 or E2 (0.1, 1, 10, 100, and 1000 μg/kg/day), or vehicle. Blood clotting time was assessed at 1, 2, 3, 4, 5, 8, and 11 days after treatment. AE2 at all doses were anticoagulant for 2-3 days after administration whereas E2 was procoagulant for 8-11 days. These opposite effects were: AE2 Emax=+29%; E2 Emax=−30%; (P<0.01). AE2 is the parent compound of the 17ß-aminoestrogens, with the largest and longest anticoagulant effect until now reported.