Abstract
The purpose of this research is to study the specific activity of our developed nasal dosage form with n-phenylacetyl-l-prolylglycine ethyl ester. The experiments were performed on 260 white outbred rats weighing 190-220 g. Experimental allergic encephalomyelitis (EAE) was induced by a single subcutaneous inoculation of an encephalitogenic mixture (EHM) in Complete Freund's Adjuvant (CFA) based on 100 mg of homologous spinal cord homogenate; 0.2 ml of CFA (the content of killed mycobacteria 5 mg/ml) and 0.2 ml of physiological saline per animal. There were five groups of animals in the study: 1) intact; 2) control - untreated with EAE, received saline solution; 3) animals with EAE that received basic treatment - methylprednisolone (MP), 3.4 mg/kg, intraperitoneally slowly in saline no more than 1/10 of the CBV rat; 4) animals with EAE treated with MP + Noopept, at a dose of 10 mg/kg; 5) animals with EAE treated with MP + Citicoline (Ceraxon, Ferrer Internacional S.A., Spain) D003U1 series, 500 mg/kg, intragastrically. The integrative functions of rats’ brain with EAE were studied using the “Open Field” method with an arena of own production with dimensions 80x80x35 cm. The study of memory was carried out using the radial labyrinth LE760 (AgnTho's, Sweden). Capture and image recording was carried out using a color video camera SSC-DC378P (Sony, Japan). Video file analysis was performed using Smartv 3.0 software (Harvard Apparatus, USA). As a result of the studies on experimental model of multiple sclerosis with a nasal gel containing ethyl ester of n-phenylacetyl-l-prolylglycine revealed the presence of normotimic activity, antidepressant and anxiolytic effects, an increase in the total activity of the central nervous system. The results obtained indicate a high neuroprotective and nootropic activity of the Noopept intranasal gel. By the degree of influence on reducing the number of errors in working memory, the Noopept gel significantly exceeds monotherapy with methylprednisolone and combination therapy with methylprednisolone and citicoline. A further study of the effect of the developed nasal gel on the morphofunctional indices of sensorimotor cortical neurons under experimental multiple sclerosis, as well as on the content of HSP70 in the animal brain, is promising.
Highlights
As a result of this in patients there is a decrease in intelligence, memory impairment, impaired behavior, emotional functions, deep and superficial sensitivity which significantly negatively affects the quality of life of patients
The experiments were performed on 260 white outbred rats weighing 190-220 g, obtained from the nursery of the Institute of Pharmacology and Toxicology of the Academy of Medical Sciences of Ukraine
There were five groups of animals in the study: 1) intact (10 rats); 2) control – untreated with EAE, received saline solution (20 rats); 3) animals with EAE that received basic treatment – methylprednisolone (MP), 3.4 mg/kg, intraperitoneally slowly in saline no more than 1/10 of the CBV rat (20 rats); 4) animals with EAE treated with MP + Noopept at a dose of 10 mg / kg (20 rats); 5) animals with EAE treated with MP + Citicoline (Ceraxon, Ferrer Internacional S.A., Spain) D003U1 series, 500 mg / kg, intragastrically (20 rats)
Summary
Нейропротективні властивості назального гелю з етиловим ефіром n-фенілацетил-lпролілгліцину на експериментальній моделі еквіваленту розсіяного склерозу. У результаті проведених досліджень на експериментальній моделі розсіяного склерозу, назального гелю з етиловим ефіром n-фенілацетил-l-пролілгліцина виявлено наявність нормотимічної активності, антидепресивної й анкіолітичної дії, збільшення загальної активності ЦНС. Перспективними є подальше вивчення впливу розробленого назального гелю на морфофункціональні показники нейронів сенсомоторної кори в умовах експериментального розсіяного склерозу, а також на утримання HSP70 у головному мозку тварин. At the department of Drug Technology, Pharmacology and Medical Formulations of Zaporizhzhya State Medical University within the framework of the research topic “Development of the composition, technology and biopharmaceutical studies of pharmacotherapeutic systems for transmucosal delivery of drugs”, as a result of complex physical, chemical, microbiological and biopharmaceutical studies, a new, gel, nasal form with an active pharmaceutical ingredient – n-phenylacetyl-l-. A generally recognized model of multiple sclerosis in laboratory animals is experimental allergic encephalomyelitis (EAE), which has multiple sclerosis-like clinical manifestations and pathogenetic mechanisms [2, 4, 6, 7, 8]
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