This study was the first to compare the neuroprotective activity of Cerebrolysin®, Actovegin® and Cortexin® in rodent models of acute and chronic brain ischemia. The neuroprotective action was evaluated in animals with acute (middle cerebral artery occlusion) or chronic (common carotid artery stenosis) brain ischemia models in male rats. Cortexin® (1 or 3 mg/kg/day), Cerebrolysin® (538 or 1614 mg/kg/day) and Actovegin® (200 mg/kg/day) were administered for 10 days. To assess the neurological and motor impairments, open field test, adhesive removal test, rotarod performance test and Morris water maze test were performed. Brain damage was assessed macro- and microscopically, and antioxidant system activity was measured in brain homogenates. In separate experiments in vitro binding of Cortexin® to a wide panel of receptors was assessed, and blood-brain barrier permeability of Cortexin® was assessed in mice in vivo. Cortexin® or Cerebrolysin® and, to a lesser extent, Actovegin® improved the recovery of neurological functions, reduced the severity of sensorimotor and cognitive impairments in rats. Cortexin® reduced the size of necrosis of brain tissue in acute ischemia, improved functioning of the antioxidant system and prevented the development of severe neurodegenerative changes in chronic ischemia model. Radioactively labeled Cortexin® crossed the blood-brain barrier in mice in vivo with concentrations equal to 6–8% of concentrations found in whole blood. During in vitro binding assay Cortexin® (10 μg/ml) demonstrated high or moderate binding to AMPA-receptors (80.1%), kainate receptors (73.5%), mGluR1 (49.0%), GABAA1 (44.0%) and mGluR5 (39.7%), which means that effects observed in vivo could be related on the glutamatergic and GABAergic actions of Cortexin®. Thus, Cortexin, 1 or 3 mg/kg, or Cerebrolysin®, 538 or 1614 mg/kg, were effective in models acute and chronic brain ischemia in rats. Cortexin® contains compounds acting on AMPA, kainate, mGluR1, GABAA1 and mGluR5 receptors in vitro, and readily crosses the blood-brain barrier in mice.

Derivatives of alpha-pyrrolidone and some derivatives of adamantane possess a wide spectrum of psychotropic activity. The synthesis of adamantane and homoadamantane derivatives of alpha-pyrrolidone and the assessment of their psychotropic activity were performed. A number of framework compounds containing a pyrrolidin-2-one fragment either in the side chain or as part of the framework system were synthesized. N-(Adamantan-1-yl)pyrrolidin-2-one (TIM-2) was obtained by the reaction of 1-bromadamantane with pyrrolidin-2-one. Homoadamantane-fused pyrrolidin-2-one (TIM-1) was obtained from β-dicarbonyl derivatives of homoadamantane. Synthesis of the starting 2-(5-oxohomoadamantyl)acetic acid was carried out by cleavage of the corresponding keto diester or cyanoketo ester of homoadamantane under the conditions of the Holler-Bauer reaction with sonication. Then, the resulting γ-keto acid was introduced into the Leuckart-Wallach reaction to obtain cis- decahydro-4,8:6,10-dimethanocyclononane[b]pyrrol-2(1H)-one (TIM-1). The psychotropic activity of the obtained compounds was evaluated in standard behavioral tests in experimental animals. Compound TIM-2 exhibited pronounced anxiolytic, antidepressant, and nootropic activity. Compound binding assays were performed by molecular docking of the synthesized compounds to the GABA-B receptor, which also showed high binding energies for TIM-2.

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Кафедра фармакологии и фармации ИНМФО, Волгоград В работе была исследована эффективность профилактического и терапевтического введения ацетилцистеина (1 г/кг, п/о) в отношении вазодилатирующей функции эндотелия сосудов головного мозга крыс после острой алкогольной интоксикации. Этанол вводили в дозе 3 г/кг (в/б). Профилактическое введение ацетилцистеина выполняли за 1 ч до введения этанола, терапевтическоепосле пробуждения животных. Неврологический дефицит оценивали по шкале Combs and D'Alecy после пробуждения животных и через 3 ч после него. Затем оценивали локальный мозговой кровоток и эндотелийзависимую вазодилатацию (стимулированную и базальную секрецию оксида азота). В работе было показано, что у крыс после острой алкогольной интоксикации уровень неврологического дефицита относительно контрольной группы был значимо ниже как при терапевтическом, так и при профилактическом введении ацетилцистеина. Терапевтическое введение ацетилцистеина после острой алкогольной интоксикации значимо не влияло на уровень мозгового кровотока и базальную секрецию оксида азота, но повышало стимулированную секрецию NO. Профилактическое введение ацетилцистеина способствовало увеличению уровня мозгового кровотока, а также значимому повышению стимулированной и базальной секреции оксида азота по сравнению с контрольной группой. Таким образом, терапевтическое и особенно профилактическое введение ацетилцистеина улучшает функциональное состояние эндотелия сосудов головного мозга после острой алкогольной интоксикации. Ключевые слова: этанол, эндотелий, мозговой кровоток, похмелье, ацетилцистеин, крысы.