RESUMEN
It is shown that 2-chloroethoxy-para-N-dimethylphosphorylacetohydrazide and N-acethylhydrazide-para-dimethylaminophenyl-2-chloroethoxyphosphorylacetic acid reliably reduce ischemia-induced depression of inotropic functions of the left ventricle in cats with experimental myocardial infarction model. The effect of both compounds can be explained by the maintenance of viability of the injured myocardium via a delay of the development of acidosis and the support of oxygen recycling in the ischemized zone. Both compounds show pronounced antiradical properties with a non-standard mechanism of action.
Asunto(s)
Acetatos/farmacología , Hidrazinas/farmacología , Isquemia Miocárdica/tratamiento farmacológico , Ácidos Fosfóricos/farmacología , Acetatos/uso terapéutico , Animales , Gatos , Modelos Animales de Enfermedad , Hidrazinas/uso terapéutico , Contracción Miocárdica/efectos de los fármacos , Isquemia Miocárdica/fisiopatología , Consumo de Oxígeno , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
In vivo and in vitro experiments revealed the neuroprotective activity of CAPAH, a representative of the new nootropic class phosphorylated carboxylic acid hydrazides. The mechanisms of this action, which were due to the membranous stabilizing activity of the drug and its affinity for glycine strychnine-sensitive sites of MMDA receptors (Ki = 8.8.10(-5) M). Six analogues of CAPAH have been also found to have affinity for these types of receptors; based on the examination of structure-affinity relationship, putative pharmacophores (only radicals of the benzene ring of a molecule in the para position exerted effects on affinity changes) were revealed. The findings give a deep insight into the mechanism of nootropic activity and open vistas for synthesizing phosphorylated carboxylic acid hydrazides as potential neuroprotective agents interacting with glycine strychnine-sensitive sites of MMDA receptor.
Asunto(s)
Acetatos/farmacología , Isquemia Encefálica/prevención & control , Hidrazinas/farmacología , Neuronas/efectos de los fármacos , Nootrópicos/farmacología , Acetatos/química , Marcadores de Afinidad/química , Marcadores de Afinidad/farmacología , Animales , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patología , Células Cultivadas , Hidrazinas/química , Ratones , Neuronas/metabolismo , Nootrópicos/química , RatasAsunto(s)
Acetatos/farmacología , Membrana Eritrocítica/efectos de los fármacos , Hemólisis/efectos de los fármacos , Hidrazinas/farmacología , Nootrópicos/farmacología , Animales , Espectroscopía de Resonancia por Spin del Electrón , Membrana Eritrocítica/química , Hipoxia/sangre , Técnicas In Vitro , Lípidos de la Membrana/química , Membranas Artificiales , Ósmosis , Fosfatidilcolinas/química , Ratas , Espectrofotometría InfrarrojaRESUMEN
Genotoxic action of four possible metabolites of the new tranquilizer phosphabenzide (acetylphosphabenzide, diphenylphosphinylacetic acid, phosphabenzide hydrazone with pyruvic acid, bis-1,2-(diphenylphosphinylacetyl)hydrazine) has been studied. These metabolites belong to slightly toxic phosphororganic compounds. The Ames Salmonella/microsomes tests performed on strains TA100 and TA98 showed that of these compounds only acetylphosphabenzide possessed mutagenic action. Metabolic activation of liver microsomes decreased the mutagenic effect. The mechanism of action of acetylphosphabenzide is likely to involve the formation of acetylhydrazine, capable of producing active electrophiles attacking DNA.
