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J Psychiatr Res ; 84: 191-199, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27756019

RESUMEN

A growing body of evidence demonstrates that quinoline compounds have attracted much attention in the field of drug development. Accordingly, 4-phenylselenyl-7-chloroquinoline (4-PSQ) is a new quinoline derivative containing selenium, which showed a potential antioxidant, antinociceptive and anti-inflammatory effect. The present study was undertaken to evaluate the anxiolytic-like properties of 4-PSQ. Mice were orally pretreated with 4-PSQ (5-50 mg/kg) or vehicle, 30 min prior to the elevated plus-maze (EPM), light-dark (LDT) or open field (OFT) tests. A time-response curve was carried out by administration of 4-PSQ (50 mg/kg) at different times before the EPM test. The involvement of glutamate uptake/release and Na+, K+-ATPase activity in the anxiolytic-like effect was investigated in cerebral cortices. In addition, the effectiveness of acute treatment with 4-PSQ was evaluated in a model of kainate (KA)-induced anxiety-related behavior. Finally, acute toxicity of this compound was investigated. 4-PSQ produced an anxiolytic-like action, both in EPM and LDT. In OFT, 4-PSQ did not affect locomotor and exploratory activities. 4-PSQ anxiolytic-like effect started at 0.5 h and remained significant up to 72 h after administration. Treatment with 4-PSQ reduced [3H] glutamate uptake, but the [3H] glutamate release and Na+, K+-ATPase activity were not altered. KA-induced anxiety-related behavior was protected by 4-PSQ pretreatment. Additionally, 4-PSQ exposure did not alter urea levels, aspartate (AST) and alanine aminotrasferase (ALT) activities in plasma. Parameters of oxidative stress in brain and liver of mice were not modified by 4-PSQ. Taken together these data demonstrated that the anxiolytic-like effect caused by 4-PSQ seems to be mediated by involvement of the glutamatergic system.


Asunto(s)
Ansiolíticos/farmacología , Ansiedad/tratamiento farmacológico , Fármacos actuantes sobre Aminoácidos Excitadores/farmacología , Compuestos de Organoselenio/farmacología , Quinolinas/farmacología , Administración Oral , Animales , Ansiolíticos/química , Ansiolíticos/toxicidad , Ansiedad/metabolismo , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Fármacos actuantes sobre Aminoácidos Excitadores/química , Fármacos actuantes sobre Aminoácidos Excitadores/toxicidad , Conducta Exploratoria/efectos de los fármacos , Conducta Exploratoria/fisiología , Ácido Glutámico/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Estructura Molecular , Actividad Motora/efectos de los fármacos , Actividad Motora/fisiología , Compuestos de Organoselenio/química , Compuestos de Organoselenio/toxicidad , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Pruebas Psicológicas , Quinolinas/química , Quinolinas/toxicidad , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Factores de Tiempo , Tritio
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