评估α2-肾上腺素能激动剂马菲定急性给药后对白种小鼠行为的影响

N. S. Kurmazov, S. A. Chervonetskiy, V. Prikhodko, Yurii I Sysoev, S. V. Okovityi
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摘要

导言。α2-肾上腺素能激动剂不仅可用作降压药和镇静剂,还可作为治疗神经系统疾病的潜在药物。先前的研究表明,该类化合物中的一种--6-氧代-1-苯基-2-(苯基氨基)-1,6-二氢嘧啶-4-醇(mafedine)--在实验条件下具有很强的神经保护作用。尽管玛菲定的开发历史悠久,但其对动物行为特征的影响仍不为人知。本研究旨在评估三种剂量(1、10 或 50 毫克/千克)的马非丁钠在三种测试中对白种小鼠行为的影响:材料和方法。实验对象为 60 只体重为 20-22 克的白色纯种雄性小鼠,随机分为 4 组(n = 15):1)对照组(0.9% 生理盐水);2)马非丁(1 毫克/千克);3)马非丁(10 毫克/千克);4)马非丁(50 毫克/千克)。所有药剂均在测试前 20 分钟通过单次腹腔注射给药。动物行为评估采用开阔地、高架迷宫和光/暗箱测试,按照常规方案进行,测试之间重新分组,测试时间间隔至少为 2 天。统计分析使用 Prism 8.0.2 软件包进行。马非啶的剂量为 1 或 10 毫克/千克时,不会影响动物在两种试验中的行为。与对照组相比,50 毫克/千克剂量的马菲定产生了抗焦虑作用,表现在高架迷宫测试中焦虑指数值的降低以及光/暗箱测试中偷看频率的增加。研究表明,剂量为 1 至 50 毫克/千克的马菲定钠盐不会对小鼠的行为产生不良影响,这表明该化合物具有良好的安全性。在最高剂量下发现的马菲定抗焦虑作用证明,该化合物不仅可以作为神经保护剂,还可以作为抗焦虑剂进行进一步研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Evaluation of the α2-adrenergic Agonist Mafedine Effects on White Outbred Mouse Behaviour Following Acute Administration
Introduction. α2-adrenergic agonists are not only used as antihypertensive and sedative agents, but are also of interest as potential medications for the treatment of neurological disorders. Previous research has shown a compound from this class, 6-oxo-1-phenyl-2-(phenylamino)-1,6-dihydropyrimidine-4-ol (mafedine), to exert strong neuroprotection under experimental conditions. Despite its long record of development, the effects of mafedine on animal behavioural characteristics remain unknown.Aim. This work was aimed at evaluating the effects of mafedine sodium at three doses (1, 10, or 50 mg/kg) on white outbred mouse behavior in three tests: Open Field, Elevated Plus Maze, and Light/Dark Box.Materials and methods. Experiments were carried out on 60 white outbred male mice weighing 20–22 g, randomized into 4 groups (n = 15): 1) control (0,9 % saline); 2) mafedine (1 mg/kg); 3) mafedine (10 mg/kg); 4) mafedine (50 mg/kg). All agents were administered via single intraperitoneal injections 20 min before testing. Animal behavior was assessed using the Open Field, Elevated Plus Maze, and Light/Dark Box tests following conventional protocols with group reassignment between tests and an inter-test time interval of at least 2 days. Statistical analysis was carried out using the Prism 8.0.2 software package.Results and discussion. At 1 or 10 mg/kg, mafedine did not affect animal behaviour in either of the tests. At 50 mg/kg, it produced an anxiolytic effect, as indicated by the decrease in the anxiety index values for the Elevated Plus Maze test as well as the increase in peeking out frequency in the Light/Dark Box test, compared to respective control values.Сonclusion. Mafedine sodium salt at doses between 1 and 50 mg/kg was shown to produce no adverse effect on mouse behaviour, indicating a good safety profile of the compound. The discovered anxiolytic effect of mafedine at the highest dose validates its further research not only as a neuroprotector, but also as an anti-anxiety agent.
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