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  • Title: In vivo profile of the anticoagulant effect of 17ß-amino-1,3,5(10)estratrien-3-ol.
    Author: Lemini C, Rubio-Póo C, Franco Y, Jaimez R, Avila ME, Medina M, Lemus AE.
    Journal: Eur J Pharmacol; 2013 Jan 30; 700(1-3):210-6. PubMed ID: 23305838.
    Abstract:
    The anticoagulant activity of 17ß-amino-1,3,5(10)estratrien-3-ol (AE(2)) was established for the first time. Experiment 1: mice groups were treated with a single subcutaneous (s.c.) AE(2) injection (0.5, 1, 2, 4, and 8 mg/100 g BW) or vehicle (propylenglycol; 0.5 ml/100 g). After 24 h, AE(2) 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 AE(2) (4 or 8 mg/100g BW) or 17ß-estradiol (E(2); 3mg/100g 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 AE(2) 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 E(2) decreased blood clotting 20% (P<0.01) and thrombin 23% (P<0.01) after 48 h. Experiment 3: for five consecutive days, mice received AE(2) or E(2) (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. AE(2) at all doses were anticoagulant for 2-3 days after administration whereas E(2) was procoagulant for 8-11 days. These opposite effects were: AE(2) Emax=+29%; E(2) Emax=-30%; (P<0.01). AE(2) is the parent compound of the 17ß-aminoestrogens, with the largest and longest anticoagulant effect until now reported.
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