In vivo profile of the anticoagulant effect of 17ß-amino-1,3,5(10) estratrien-3-ol
Por:
Lemini C., Rubio-Póo C., Franco Y., Jaimez R., Avila, ME, Medina M., Lemus, AE
Publicada:
30 ene 2013
Categoría:
Pharmacology
Resumen:
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). AE 2 is the parent compound of the 17ß-aminoestrogens, with the largest and longest anticoagulant effect until now reported. © 2012 Elsevier B.V.
Filiaciones:
Univ Nacl Autonoma Mexico, Fac Med, Dept Farmacol, Mexico City 04360, DF, Mexico
Univ Nacl Autonoma Mexico, Fac Estudios Super Zaragoza, Mexico City 04360, DF, Mexico
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