Оцінка нейропротекторної активності метадоксину на моделі хемоіндукованих судом, викликаних коразолом, бімегридом і стрихніном

Abstract

Проведена оценка нейропротекторного действия метадоксина на модели хемоиндуцированных судорог, вызванных коразолом, бимегридом и стрихнином. Установлено, что метадоксин при длительном введении мышам (7 суток, 135 и 270 мг/кг интрагастрально) статистически достоверно повышает минимальные дозы хемоконвульсантов, взаимодействующих с ГАМК-барбитуратным рецепторным комплексом. Влияние длительного введения метадоксина на судороги, вызванные стрихнином, отсутствует. С помощью дисперсионного анализа установлено, что воздействие на противосудорожный эффект метадоксина после его длительного введения повышается с 0,65 (при дозе 135 мг/кг) до 0,8 (270 мг/кг).

Metadoxine is positioned as a drug with predominantly hepatoprotective action, but, taking into account its mechanism of action, it is also important to study it as a neuroprotective/neuroactive compound in order to expand the limits of its use in clinical practice. Aim: evaluation of the neuroprotective effect of metadoxin in the model of chemically induced seizures caused by pentylenetetrazole, bemegride and strychnine. Materials and methods of research. To evaluate the effect of metadoxine on the CNS inhibitory systems, a model of seizures caused by chemoconvulsants was chosen. The development of seizures during their intravenous infusion is concentration-dependent, and the use of various convulsive agents allows almost isolated monitoring of the participation of metadoxine in individual inhibitory processes. Results. The anticonvulsant action of metadoxine varies considerably depending on which convulsive agent is used as a chemoconvulsant. Thus, when using convulsive agents that affect the functions of GABA-BD-barbiturate receptor complex (pentylenetetrazole and bemegrid), the anticonvulsant effect is quite significant and in some respects probably differs from the control values. The values of strychnine doses during its intravenous infusion after long-term administration of metadoxin do not experience statistically significant differences from the indicators of the control group of animals (in absolute terms, even a slight decrease is observed). Conclusions. It was found that metadoxine with long-term administration to mice (7 days, 135 and 270 mg/kg intragastric) statistically significantly increases the minimum dose of chemoconvulsants that interact with GABA-barbiturate receptor complex. There is no effect of long-term administration of metadoxine on seizures caused by strychnine.