Investigation of antiparkinsonian activity of new imidazole-4,5-dicarboxylic acid derivatives on the experimental model of catalepsy

Q3 Pharmacology, Toxicology and Pharmaceutics
Vladimir D. Dergachev, E. E. Yakovleva, M. A. Brusina, E. Bychkov, L. B. Piotrovskiy, P. Shabanov
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引用次数: 1

Abstract

Introduction: To study the antiparkinsonian activity of new ligands of the glutamate NMDA receptor complex – 1,2–substituted imidazole-4,5-dicarboxylic acids – on an experimental model of catalepsy caused by haloperidolintraabdominal injections in rats. Materials and methods: The experiments were performed on Wistar rats weighing 300-350 g, obtained from the Rappolovo nursery of the Russian Academy of Medical Sciences (Leningrad Region). The animals were kept in standard plastic cages in vivarium conditions with free access to water and food at a temperature of 22±2 °C and in the experiment were divided into several groups (6 animals each). All the experiments were carried out in the autumn-winter period. The animals were kept in accordance with the rules of laboratory practice (GLP), regulatory documents ”Sanitary Rules for the Device, Equipment and Maintenance of Vivarium” and the Order of the Ministry of Health and Social Development of the Russian Federation dated 23.08.2010 No. 708n “On Approval of the Rules of Laboratory Practice”. Imidazole-dicarboxylic acid derivatives (IEM-2295, IEM-2296) were injected intraperitoneally at doses from 5 mg/kg to 40 mg/kg simultaneously with haloperidol at a dose of 1 mg/kg, after which the duration and severity of catalepsy were evaluated after 30, 60, 120 minutes from 0 to 6 points according to the Morpurgo method. Results: The severity of catalepsy with the injection of IEM-2295 decreased on average to 3 points, while in the control group it remained at the level of 6 points throughout the observation. However, the severity of catalepsy with the introduction of IEM-2296 decreased to an average of 4 points, but the effect itself lasted longer than with the introduction of IEM-2295. Thus, it was noted that by the 120th minute of observation, the severity of catalepsy in rats receiving the IEM-2295 compound averaged 5 points, whereas in animals receiving IEM-2296 – 3 points. Discussion: Basing on the results of our work and similar experiments, we can conclude that the studied compounds, which are not channel blockers, have an active effect on dopaminergic neurotransmission, because of which the symptoms of catalepsy that occur when haloperidol is injected to rats were stopped to one degree or another. Conclusion: The studied substances exhibit antiparkinsonian activity on an experimental haloperidol model of catalepsy in rats and are promising for development as potential therapies for neurodegenerative diseases. Further study of these compounds and other ligands from the NMDA-blocker group in a wider sample on the catalepsy model, as well as on other models of Parkinsonism, is required. Graphical Abstract
新型咪唑-4,5-二羧酸衍生物在催化实验模型上抗帕金森病活性的研究
前言:研究谷氨酸NMDA受体复合物的新配体- 1,2 -取代咪唑-4,5-二羧酸对氟哌啶酮腹腔注射致大鼠猝倒的抗帕金森活性。材料和方法:实验用Wistar大鼠,体重300-350 g,来自俄罗斯医学科学院(列宁格勒地区)Rappolovo托儿所。实验动物饲养在标准塑料笼内,在22±2℃的条件下自由饮水和进食。实验动物分为几组,每组6只。所有实验均在秋冬季节进行。这些动物是按照实验室操作规则(GLP)、规范性文件“试管设备、设备和维护卫生规则”以及俄罗斯联邦卫生和社会发展部2010年8月23日第708n号“关于批准实验室操作规则”的命令饲养的。将咪唑-二羧酸衍生物(IEM-2295、IEM-2296)以5 ~ 40 mg/kg的剂量与氟哌啶醇1 mg/kg的剂量同时腹腔注射,分别于0 ~ 6点30、60、120分钟后,根据Morpurgo法评价其持续时间和严重程度。结果:注射IEM-2295后,患者的麻痹程度平均降低至3分,而对照组在整个观察过程中保持在6分水平。然而,引入IEM-2296后,麻痹的严重程度下降到平均4分,但效果本身持续的时间比引入IEM-2295时更长。因此,我们注意到,在观察第120分钟时,接受IEM-2295化合物的大鼠的麻痹严重程度平均为5分,而接受IEM-2296 - 3分的动物。讨论:根据我们的工作和类似的实验结果,我们可以得出结论,所研究的化合物,不是通道阻滞剂,对多巴胺能神经传递有积极的影响,因为氟哌啶醇注射给大鼠时发生的猝厥症状在某种程度上停止了。结论:所研究的物质在氟哌啶醇猝倒大鼠实验模型中表现出抗帕金森活性,有望成为神经退行性疾病的潜在治疗药物。这些化合物和来自nmda阻断剂组的其他配体在更广泛的样本中对猝睡模型以及其他帕金森模型进行进一步的研究是必要的。图形抽象
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来源期刊
Research Results in Pharmacology
Research Results in Pharmacology Medicine-Pharmacology (medical)
CiteScore
1.50
自引率
0.00%
发文量
32
审稿时长
12 weeks
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