[Behavioral and neuroreceptor effects of the racetam derivative GIZh-290 in mouse experimental attention deficit model].

Q3 Biochemistry, Genetics and Molecular Biology Biomeditsinskaya khimiya Pub Date : 2022-11-01 DOI:10.18097/PBMC20226805367
G I Kovalev, N A Sukhorukova, E V Vasileva, E A Kondrakhin, R M Salimov, V B Narkevich, V S Kudrin
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Abstract

Behavioral and neurochemical effects of the new racetam derivative GIZh-290 were studied in a mouse attention deficit model (the ED-Low animals subpopulation selected during preliminary behavioral typing in the "closed enriched cross maze" test). Subchronic administration of GIZh-290 (1 mg/kg, 3 mg/kg and 5 mg/kg, intraperitoneally, for 6 days), increased the initially low level of attention in ED-Low animals; the highest selectivity was observed at a dose of 3 mg/kg. Radioligand analysis showed that at this dose, the drug changed density (Bmax) of D2 and GABAB receptors as markers in the pre-frontal cortex of the ED-Low subpopulation to Bmax values observed in the ED-High subpopulation. In the prefrontal cortex of the ED-Low rodents treated with GIZh-290 in dose of 3 mg/kg, there was a normalization of tissue concentrations of both dopamine itself (DA) and its intra- and extracellular metabolites (DOPA/DA and HVA/DA). The obtained results indicate the effectiveness of the studied drug for pharmacotherapy of attention deficit in experimental modeling and impact on potential molecular targets identified in the study.

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[消拉西坦衍生物giz -290在小鼠实验注意缺陷模型中的行为和神经受体效应]。
新消旋坦衍生物giz -290在小鼠注意缺陷模型(在“封闭富集交叉迷宫”试验中选择的ED-Low动物亚群进行初步行为分型)中研究了行为和神经化学效应。亚慢性给药giz -290 (1mg /kg、3mg /kg和5mg /kg,腹腔注射,持续6天)可提高ED-Low动物最初的低注意力水平;在剂量为3 mg/kg时观察到最高的选择性。放射配体分析显示,在该剂量下,药物将ED-Low亚群前额叶皮层D2和GABAB受体作为标记物的密度(Bmax)改变为ED-High亚群所观察到的Bmax值。以3 mg/kg剂量的giz -290处理ED-Low啮齿动物的前额叶皮层,多巴胺本身(DA)及其细胞内和细胞外代谢物(DOPA/DA和HVA/DA)的组织浓度均恢复正常。实验结果表明了所研究药物对注意缺陷药物治疗的有效性,以及对研究中确定的潜在分子靶点的影响。
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来源期刊
Biomeditsinskaya khimiya
Biomeditsinskaya khimiya Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)
CiteScore
1.30
自引率
0.00%
发文量
49
期刊介绍: The aim of the Russian-language journal "Biomeditsinskaya Khimiya" (Biomedical Chemistry) is to introduce the latest results obtained by scientists from Russia and other Republics of the Former Soviet Union. The Journal will cover all major areas of Biomedical chemistry, including neurochemistry, clinical chemistry, molecular biology of pathological processes, gene therapy, development of new drugs and their biochemical pharmacology, introduction and advertisement of new (biochemical) methods into experimental and clinical medicine etc. The Journal also publish review articles. All issues of journal usually contain invited reviews. Papers written in Russian contain abstract (in English).
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