title: In vivo profile of the anticoagulant effect of 17ß-amino-1,3,5(10)estratrien-3-ol.
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.
authors.affiliation: Departamento de Farmacología, Facultad de Medicina, UNAM. Av. Universidad No. 3000, Ciudad Universitaria, Colonia Copilco Universidad, Delegación Coyoacán, Mexico DF, CP 04360, Mexico. clemini@unam.mx
authors.forename: Cristina
authors.initials: C
authors.lastname: Lemini
authors.forename: Consuelo
authors.initials: C
authors.lastname: Rubio-Póo
authors.forename: Yanira
authors.initials: Y
authors.lastname: Franco
authors.forename: Ruth
authors.initials: R
authors.lastname: Jaimez
authors.forename: María Estela
authors.initials: ME
authors.lastname: Avila
authors.forename: Martha
authors.initials: M
authors.lastname: Medina
authors.forename: Ana Elena
authors.initials: AE
authors.lastname: Lemus
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects; D001780:Blood Coagulation Tests; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology*; D005340:Fibrinogen / Q000378:metabolism; D008297:Male; D051379:Mice
chemical_list: C582662:17-amino-1,3,5(10)estratrien-3-ol; D000925:Anticoagulants; D004963:Estrenes; D004958:Estradiol; D005340:Fibrinogen