Антидепрессивная Активность И Потенциальные Механизмы Действия Производного Диазепинобензимидазола Даб-19

Спасов, А. А.; Maltsev, D. V.; Мирошников, М. В.; Таран, А. С.; Нурмагомедова, Б. Р.; Skripka, Maria O.; Кузьменко, Т. А.; Морковник, А. С.; Divaeva, L. N.

doi:10.30906/0869-2092-2020-83-4-31-36

Cited by 4 publications

(3 citation statements)

References 7 publications

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“…It can indicate either pronounced emotionality in the animals, which is not confirmed by the number of boluses as one of the observed parameters, or a positive effect on the cognitive aspect of the experimental rodents` behavior, which is supported by a distinct anxiolytic effect of DAB-19 in previous study (Spasov et al 2018).The suppression of natural fear of open spaces allows animals to show interest in exploring new territories. The anxiolytic effect of DAB-19 is also confirmed by a high number of entries to the central lit area, rarely recorded short-term self-groomings (which is known to indicate the nervous state of the animal) and a large number of acts of prolonged groomings (which is consistent with the results of screening and in-depth studies of the anti-anxiety activity of the compound) (Spasov et al 2018;Spasov et al 2020).…”

Section: Resultssupporting

confidence: 66%

Influence of Diazepino[1,2-a]benzimidazole derivative (DAB-19) on behavioral aspects of animals

Maltsev¹,

Spasov²,

Мирошников³

et al. 2020

RRP

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Introduction: Diazepino[1,2-a]benzimidazole derivatives showed anxiolytic (EPM, L/D box, Vogel test), antidepressant (Tail Suspension test, Porsolt test), anticonvulsant (Pentylenetetrazole-Induced seizures) and analgesic (Tail-Flick, Hot Plate) actions, which were described earlier (Spasov et al. 2020). 11-(4-tert-butylbenzyl)-2,3,4,5-tetrahydro[1,3]diazepino[1,2-a]benzimidazole hydrobromide (compound DAB-19) has evident anxiolytic, antidepressant and anticonvulsant effects. In the present study, compound DAB-19 was screened for its influence on animals` behavior patterns, such as aggression, obsessive-compulsive behavior, emotional lability, and unsociability. Materials and methods: 112 outbred white animals (rats and mice) were used. Compound DAB-19 (2.34 mg/kg, p.o.) and diazepam (2 mg/kg, p.o.) were injected to the treatment groups. Using an Open Field (OF) test, we evaluated a spontaneous motor activity, a search activity of mice and a degree of their emotionality. During a Marble Burying (MB) test, we monitored anxiolytic and anticompulsive effects of DAB-19. Using a Resident-intruder (RI) test, we evaluated a degree of aggression in the experimental animals, properties of their social interaction, as well as defensive and individual behavior. Results and discussion: Compound DAB-19 has positive influence on the search activity, mood stabilizing activity and antiaggressive actions. Administration of both DAB-19 (2.34 mg/kg, p.o.) and diazepam (2 mg/kg, p.o.) reduced anxiety-like behavior in OP, RI and MB tests, as indicated by a significantly increased number of entries to the center of OP; a decreased number of marbles buried in MB and reduced aggressive behavior in RI. It was stated that using DAB-19 leads to a decrease in affective reactions of the animals – aggression, obsessive-compulsive behavior, neurotic condition and emotional instability. Conclusions: The compound (DAB-19) produces anxiolytic-like effects, compared with those of diazepam, in various anxiety paradigms.

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Section: Resultssupporting

confidence: 66%

Influence of Diazepino[1,2-a]benzimidazole derivative (DAB-19) on behavioral aspects of animals

Maltsev¹,

Spasov²,

Мирошников³

et al. 2020

RRP

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“…In previous studies, the products of the combination of a diazepine scaffold with benzimidazole moiety were studied -2,3,4,5-tetrahydro[1,3]diazepino[1,2-a]benzimidazole hydrochlorides under the general code DAB (Spasov et al 2018). For various representatives of this series of compounds, a wide range of neurotropic effects have been noted -anxiolytic, antidepressant, anticonvulsant, hypnotic, and some others (Miroshnikov et al 2020, Spasov et al 2020a; however, no adverse drug reactions of the benzodiazepine group were noted for them. Further search for effective anxiolytics among the combinations of the benzodiazepine core structure with the hit structures of various chemical classes seems promising: in the present study, the products of the combina-tion of 1,2,4-triazole and 2,3-benzodiazepine, derivatives of 6-(4-methoxyphenyl)-7H-[1,2,4]triazolo [3,4-A][2,3] benzodiazepine under the general laboratory code RD were investigated.…”

Section: Introductionmentioning

confidence: 99%

Screening of anxiolytic properties and analysis of structure-activity relationship of new derivatives of 6-(4-methoxy)-7H-[1,2,4]triazolo[3,4-a][2,3]benzodiazepine under the code RD

Skripka¹,

Spasov²,

Maltsev³

et al. 2021

RRP

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Introduction: Searching for new compounds with anti-anxiety activity resulting from the combination of privileged scaffolds is a promising direction in medicinal chemistry and in the development of new drugs. Anxiolytic potential and cytotoxic properties of previously synthesized molecules, containing fragments of 2,3-benzodiazepine and 1,2,4-triazole – 6-(4-methoxyphenyl)-7H-[1,2,4]triazolo[3,4-A][2,3]benzodiazepines under the generic code RD were studied. Materials and methods: Screening for anxiolytic activity was performed on elevated plus maze (EPM) and open field (OF) test models. Structural and functional analysis of the anti-anxiety activity of the studied substances was carried out. A degree of muscle relaxant effect of the substances was assessed in the tests Grid, Wire, and Rotarod. A cytotoxicity study of RD compounds was carried out using an MTT assay on human hepatocellular carcinoma cells HepG2. Results and discussion: For a number of novel triazolo[3,4-a][2,3]benzodiazepine derivatives, a prominent anxiolytic activity was manifested in terms of EPM test. The results of OF test were consistent with the obtained data and confirmed the presence of the sought activity in the leading compounds. There was no significant effect on muscle tone for the compounds under study. It was observed that RD compounds possessed no cytotoxic properties and were safe for further studies in vivo. Conclusion: Among the new derivatives of 6-(4-methoxyphenyl)-7H-[1,2,4]triazolo[3,4-a][2,3]benzodiazepine under the code RD, substances (RD-4, 12, 13) with a high anxiolytic activity comparable to diazepam and tofisopam were found. The most promising compound is RD-4 due to its pronounced anxiolytic and low cytotoxic properties.

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“…Назначаемые антидепрессанты и транквилизаторы имеют ряд недостатков: возможен длительный латентный период формирования терапевтического эффекта, а также его недостаточная широта и стойкость, риск токсических эффектов при передозировке, высокая вероятность развития побочных эффектов, что часто становится причиной отказа от назначаемой терапии [3]. Эти факторы делают актуальными поиск и разработку психотропных препаратов, обладающих поливалентным действием, сочетающих собственно антидепрессивную активность со способностью устранять тревожную симптоматику, положительно влиять на интеллектуально-мнестические функции пациента, с быстрым развитием психотропного эффекта и достаточной терапевтической широтой [4].…”

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Antidepressant Effect of Adamantane Derivative of Gaba on a Social Model of Depression

Kovalev¹,

Бакулин²,

Куркин³

et al. 2021

СПНО (MPSE)

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Цель исследования -изучить выраженность антидепрессантного действия адамантанового производного ГАМК на модели социальной депрессии. Формирование депрессии осуществляли в модели социального стресса на самцах мышей. После 10 дней моделирования у животных оценивали выраженность тревожно-депрессивного состояния в следующих стандартных поведенческих тестах: Социальное взаимодействие, Приподнятый крестообразный лабиринт, Плавание по Porsolt и Подвешивание мышей за хвост. После тестирования животных распределяли в группы, а затем в течение 10 дней им вводили 0,9 % раствор NaCl (контроль), адамантановое производное ГАМК или имипрамин, при этом моделирование депрессивно-подобного состояния не прекращали. На заключительном этапе тестирование животных повторяли. У животных контрольной группы было выявлено статистически значимое повышение тревожности и выраженности поведенческого отчаяния в сравнении с интактной группой, а также выраженное снижение социализации. В группах, животным которых вводили адамантановое производное ГАМК или имипрамин, отмечалась значительно меньшая выраженность признаков депрессии, при этом под влиянием производного ГАМК отмечали более низкий уровень тревоги и лучшие показатели социализации. Исследуемое адамантановое производное ГАМК при курсовом введении животным с депрессией, вызванной 20-дневной социальной конфронтацией, сопоставимо с имипрамином устраняло проявление депрессии и более выраженно снижало тревогу и нормализовало социализацию депрессированных животных.

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Антидепрессивная Активность И Потенциальные Механизмы Действия Производного Диазепинобензимидазола Даб-19

Cited by 4 publications

References 7 publications

Influence of Diazepino[1,2-a]benzimidazole derivative (DAB-19) on behavioral aspects of animals

Influence of Diazepino[1,2-a]benzimidazole derivative (DAB-19) on behavioral aspects of animals

Screening of anxiolytic properties and analysis of structure-activity relationship of new derivatives of 6-(4-methoxy)-7H-[1,2,4]triazolo[3,4-a][2,3]benzodiazepine under the code RD

Antidepressant Effect of Adamantane Derivative of Gaba on a Social Model of Depression

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