RESUMO
The effective diuretic dose of 5-HT3 receptor blocker RU-63 (1 mg/kg) was found in experiments on white rats. It is established that the diuretic and saluretic effects of compound RU-63 increase on the background of impact of the gravitational factor. Compound RU-63 (1 mg/kg, subcutaneously) administered daily under hypergravity conditions (3 g in the direction of centrifugal force toward the kidneys) in animals with model ischemic acute renal failure increased excretory function of kidneys, glomerular filtration rate, and creatininuresis (on average by 180%; p < 0.05), and decreased serum creatinine, urinary excretion of protein, lactate dehydrogenase, and g-glutamyl transferase (on average by 49%; p < 0.05) as compared to the untreated control. Under similar conditions, the diuretic hydrochlorothiazide (in a dose of 20 mg/kg, intragastric) produced a more pronounced creatininuretic action than that of RU-63 (by 358%; p < 0.05).
Assuntos
Injúria Renal Aguda/tratamento farmacológico , Benzimidazóis/farmacologia , Diuréticos/farmacologia , Substâncias Protetoras/farmacologia , Proteinúria/tratamento farmacológico , Antagonistas do Receptor 5-HT3 de Serotonina/farmacologia , Injúria Renal Aguda/fisiopatologia , Injúria Renal Aguda/urina , Animais , Creatinina/urina , Taxa de Filtração Glomerular , Hidroclorotiazida/farmacologia , Rim/efeitos dos fármacos , Rim/fisiopatologia , L-Lactato Desidrogenase/urina , Potássio/urina , Proteinúria/fisiopatologia , Proteinúria/urina , Ratos , Receptores 5-HT3 de Serotonina/metabolismo , Sódio/urina , gama-Glutamiltransferase/urinaRESUMO
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.
Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Losartan/farmacologia , Saralasina/farmacologia , Animais , Avaliação Pré-Clínica de Medicamentos , Feminino , Técnicas In Vitro , Concentração Inibidora 50 , Masculino , Contração Muscular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Veia Porta/efeitos dos fármacos , Veia Porta/fisiologia , Ratos Wistar , Vasoconstrição/efeitos dos fármacosRESUMO
We studied the ability of predominantly 5-HT2A receptor antagonists to prevent a serotonin-induced change of blood flow in the carotid vessels of rats with experimental serotonin-induced spasm. Ritanserin, ketanserin, and 5-HT2A receptor antagonist RU-476 reduced the effect of serotonin on the blood fl ow velocity in the internal carotid artery by 2.3, 1.7, and 2.6 times, respectively.
