Depression is a leading cause of disability and reduced work capacity worldwide. The monoamine theory of the pathogenesis of depression has remained dominant for many decades, however, drugs developed on its basis have limited efficacy. Exploring alternative mechanisms underlying this pathology could illuminate new avenues for pharmacological intervention. Targeting glutamatergic pathways in the CNS, particularly through modulation of NMDA and AMPA receptors, demonstrates promising results. This review presents some existing drugs with glutamatergic activity and novel developments based on it to enhance the efficacy of pharmacotherapy for depressive disorders.

Depression is a leading cause of disability and reduced work capacity worldwide. The monoamine theory of the pathogenesis of depression has remained dominant for many decades, however, drugs developed on its basis have limited efficacy. Exploring alternative mechanisms underlying this pathology could illuminate new avenues for pharmacological intervention. Targeting glutamatergic pathways in the CNS, particularly through modulation of NMDA and AMPA receptors, demonstrates promising results. This review presents some existing drugs with glutamatergic activity and novel developments based on it to enhance the efficacy of pharmacotherapy for depressive disorders.

The interactions of compound ZDM-81 with some CNS neurotransmitter systems were studied using in vivo methods to evaluate the interaction of the compound with dopaminergic (catalepsy, induced with haloperidol), adrenergic (clonidine hypothermia), GABAergic (test of interaction with flumazenil) and serotonergic (5-hydroxytryptophan hyperkinesis) systems. It was shown that the ZDM-81 compound is able to prolong and potentiate the effects of 5-hydroxytryptophan, reduces catalepsy caused by haloperidol, does not affect the hypothermic effect of clonidine, and the effect of the ZDM-81 compound is blocked by flumazenil. Thus, for the studied substance, a serotonergic, GABAergic, and weak dopaminergic pathway for the realization of the action was shown, which requires further research.

The paper presents the results of studying the toxicological profile of a new pharmaceutical substance RU891 with antithrombogenic properties. The minimum toxic dose (TDmin) for RU-891 by peroral administration is 230 mg/kg < TDmin ≤ 460 mg/kg. In experiments on the acute toxicity of the compound RU-891, the nature and severity of its damaging effect on the body of experimental animals were established and the safety of its action was evaluated. When studying the toxic effect of the test sample, the tolerated and toxic doses of RU-891 were determined, and the most sensitive organs and systems of the body were identified.

For the substance under the code DAB-21, a pronounced neuropsychotropic potential was previously shown. In this study, possible directions of the influence of the studied substance on basic mediator systems of the CNS are considered. According to the results of the study, a benzodiazepine-like effect of DAB-21 was found in the «Elevated plus maze» test with flumazenil, as well as potentiation of the effects of phenamine, and some serotoninergic effect in the test with 5-GTP, and a weak a2-adrenoblocking effect, revealed using the «Clofelinic hypothermia» test. There was also a D2-activating effect according to the haloperidol test, a weak M-anticholinergic effect in the arecoline test. Some MAO-inhibitory effect was found, suggested by antagonism with reserpine, as well as the results of the L-DOPA test. The compound did not interact with nicotine and apomorphine. The neurotransmitter profile of the compound DAB-21 is of interest for further study and clarification of the mechanism of action of the substance.

This article presents a review of studies of new pharmacological substances in the aspect of their anxiolytic activity. These substances are derivatives of various chemical classes. The variety of synthesized substances described in this article is a combination of the most interesting and promising projects at the moment. According to the current trend, a further detailed preclinical study of chemical compounds with a multitarget mode of action is an extremely relevant issue for researchers in the areas of pharmacology and medicine.

— This paper presents a study of the anxiolytic activity of compounds that belong to two classes of chemical groups: derivatives of 11 H -2,3,4,5-tetrahydro[1,3]diazepino[1,2- a ]benzimidazole (BIF) and derivatives of 2-mercaptobenzimidazole (AZH). The study has revealed that the studied compounds exhibit different degrees of tranquilizing action. The most potent anxiolytics were compounds BIF-66 and AZH-57. These compounds hold promise for an in-depth study of their neuropsychotropic profile.

Изучена антидепрессивная активность 11-[4-трет-бутилбензил]-2,3,4,5-тетрагидро[1,3]диазепино[1,2-a]-бензимидазола гидробромида (ДАБ-19), и его возможных взаимодействий с ГАМК-рецепторами и основными катехоламинами ЦНС, а также моноаминоксидазной активности. По результатам проведенного исследования показано, что ДАБ-19 в дозе 2,34 мг/кг обладает умеренной антидепрессивной активностью на модели «Принудительное плавание по Porsolt», (78,0 ± 7,30) с для ДАБ-19 и (98,32 ± 11,54) с для группы контроля, и «Подвешивание за хвост», (110,1 ± 12,67) с для ДАБ-19 и (168,6 ± 10,2) с для контроля, на мышах (p ≤ 0,05). По результатам тестов «Апоморфиновая стереотипия» и «Стереотипия, обусловленная введением L-ДОФА» не было выявлено дофаминергической и моноаминоксидазной активности ДАБ-19 (p ≤ 0,05). Предположено наличие α2-адреноблокирующего и серотонинактивирующего действия изучаемой субстанции в тестах «5-Гидрокситриптофановый гиперкинез» и «Клофелиновая гипотермия». Антагонизм ДАБ-19 в дозе 2,34 мг/кг с флумазенилом (1 мг/кг) свидетельствует о связи психотропной активности ДАБ-19 с ГАМК-бензодиазепиновым рецепторным комплексом: время, проведенное животными в светлом рукаве для ДАБ-19 составило (78,6 ± 12,13) с, для ДАБ-19 + флумазенил — (6,7 ± 4,59) с (p ≤ 0,05).

Изучена анксиолитическая активность производного 11-(4-трет-бутилбензил)- и фенацилзамещённого 2,3,4,5-тетрагидро[1,3]диазепино[1,2-a]бензимидазола (ДАБ-19) в условиях тестов «Приподнятый крестообразный лабиринт», «Тревожно-фобическое состояние» и «Наказуемое взятие воды по Vogel». Соединение ДАБ-19 в дозе 2,34 мг/кг вводили крысам-самцам внутрижелудочно за 30 мин до начала каждого тестирования. Было показано, что данные животных группы ДАБ-19 по показателям противотревожной активности в проведенных тестах превосходили таковые для группы контроля и находились на уровне препарата сравнения феназепама (0,1 мг/кг, внутрижелудочно, за 30 мин до начала тестов, p ≤ 0,05), что позволяет сделать вывод об анксиолитическом эффекте ДАБ-19, а также подтверждает результаты ранее проведенных скрининговых исследований [14]. Вещество ДАБ-19 рассматривается как потенциальный «дневной» анксиолитик для коррекции ряда тревожно-фобических расстройств, таких как генерализованное тревожное, обсессивно-компульсивное и посттравматическое стрессовое расстройство.

НЕЙРОТОКСИКОЛОГИЧЕСКИЕ СВОЙСТВА СОЕДИНЕНИЯ РУ-891 С АНТИТРОМБОГЕННОЙ АКТИВНОСТЬЮ А.А. Спасов , А.Ф. Кучерявенко, Д.В. Мальцев , М.В. Мирошников, В.С. Сиротенко, К.Т. Султанова, К.А. Гайдукова, М.О. Скрипка ФГБОУ ВО «Волгоградский государственный медицинский университет» Министерства здравоохранения Российской Федерации, кафедра фармакологии и биоинформатики; ГБУ «Волгоградский медицинский научный центр», Лаборатория экспериментальной фармакологии