RESUMO
Antithrombotic properties of a new P2Y1 receptor antagonist N-[(1-morpholinopropyl-amino)- carbonyl-2-(1-ethyl-1H-indole-3-yl)-vinyl]-4-methylphenyl-amide hydrochloride, substance Sbt-119, and reference drug ticlopidine were studied on experimental models of arterial and systemic thromboses. Substance Sbt-119 was 39.9% (p<0.05) more potent than ticlopidine in producing the antithrombotic effect. Moreover, substance Sbt-119 was shown to increase the survival rate of animals after systemic treatment with ADP (by 20%, p<0.0001). This substance decreased the number of mural thrombi and reduced the severity of hemodynamics disturbances in the organs during systemic thrombosis.
Assuntos
Fibrinolíticos/administração & dosagem , Indóis/administração & dosagem , Morfolinas/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Trombose/tratamento farmacológico , Administração Oral , Animais , Animais não Endogâmicos , Avaliação Pré-Clínica de Medicamentos , Pulmão/patologia , Masculino , Camundongos , Ratos , Ticlopidina/farmacologiaRESUMO
We developed and tested an experimental model to study in vitro the type 1 angiotensin antagonistic activity of compounds on the isolated portal vein of rats. The reliability of this method was confirmed in tests with saralasin (nonselective antagonist of angiotensin receptors) and losartan (selective antagonist of type 1 angiotensin receptors) in concentrations of 10(-9)-10(-5) mol/liter. The half-maximal inhibitory concentrations (IC50) of these substances were calculated.
