纳洛酮、地西泮和槲皮素对慢性曲马多急性发作和镇静作用的实验研究。

IF 4.7 2区 心理学 Q1 BEHAVIORAL SCIENCES Behavioral and Brain Functions Pub Date : 2021-05-29 DOI:10.1186/s12993-021-00178-w
Samaneh Nakhaee, Khadijeh Farrokhfall, Ebrahim Miri-Moghaddam, Mohsen Foadoddini, Masoumeh Askari, Alireza Amirabadizadeh, Jeffrey Brent, Bruno Megarbane, Omid Mehrpour
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引用次数: 2

摘要

背景:曲马多是一种应用广泛的合成阿片类药物。大量的研究以前集中在这种药物的神经效应上,而各种治疗方法减少相关副作用的功效尚未得到很好的研究。本研究旨在评价纳洛酮、地西泮和槲皮素对曲马多过量诱导的雄性大鼠癫痫发作和镇静水平的保护作用。方法:选用平均体重200 ~ 250 g的雄性Wistar大鼠72只。这些大鼠被随机分为八组。曲马多以25 mg/kg/天的初始剂量腹腔注射。第14天,曲马多以75 mg/kg剂量单独或与纳洛酮、地西泮、槲皮素(急慢性)单独或联合注射。最后一天监测大鼠6小时,观察6小时内癫痫发作次数、持续时间和严重程度(以拉辛标准)。镇静水平也根据4点标准进行评估,范围从0到3。数据在SPSS软件中使用Kruskal-Wallis、卡方、回归分析和广义估计方程(GEE)检验进行分析。结果:与曲马多单独使用相比,纳洛酮-地西泮联合使用降低了癫痫发作的次数、严重程度和累积持续时间,并且比其他治疗更大程度地降低了高强度癫痫发作的次数(3,4级)。单独纳洛酮减少了癫痫发作的次数和持续时间,但增加了轻度癫痫发作的次数(2级)。地西泮减少了癫痫发作的严重程度和持续时间。然而,它增加了轻度癫痫发作的次数(2级)。与单独曲马多组相比,急性槲皮素组表现出更高的轻度(2级)和中度(3级)癫痫发作的次数。长期服用槲皮素显著增加轻度癫痫发作的次数。在GEE模型中,各组小鼠的镇静水平均高于单纯生理盐水组(P)。结论:纳洛酮联合地西泮治疗急慢性曲马多中毒比单用曲马多能有效降低大部分癫痫发作变量。然而,没有一种治疗方法能改善镇静水平。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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The effects of naloxone, diazepam, and quercetin on seizure and sedation in acute on chronic tramadol administration: an experimental study.

Background: Tramadol is a widely used synthetic opioid. Substantial research has previously focused on the neurological effects of this drug, while the efficacy of various treatments to reduce the associated side effects has not been well studied. This study aimed to evaluate the protective effects of naloxone, diazepam, and quercetin on tramadol overdose-induced seizure and sedation level in male rats.

Methods: The project was performed with 72 male Wistar rats with an average weight of 200-250 g. The rats were randomly assigned to eight groups. Tramadol was administered intraperitoneally at an initial dose of 25 mg/kg/day. On the 14th day, tramadol was injected at 75 mg/kg, either alone or together with naloxone, diazepam, and quercetin (acute and chronic) individually or in combination. The rats were monitored for 6 h on the last day, and the number, the duration, and the severity of seizures (using the criteria of Racine) were measured over a 6-h observation period. The sedation level was also assessed based on a 4-point criterion, ranging from 0 to 3. Data were analyzed in SPSS software using Kruskal-Wallis, Chi-square, regression analysis, and generalized estimating equation (GEE) tests. The significance level was set at P < 0.05.

Results: The naloxone-diazepam combination reduced the number, severity, and cumulative duration of seizures compared to tramadol use alone and reduced the number of higher-intensity seizures (level 3, 4) to a greater extent than other treatments. Naloxone alone reduced the number and duration of seizures but increased the number of mild seizures (level 2). Diazepam decreased the severity and duration of seizures. However, it increased the number of mild seizures (level 2). In comparison with the tramadol alone group, the acute quercetin group exhibited higher numbers of mild (level 2) and moderate (level 3) seizures. Chronic quercetin administration significantly increased the number of mild seizures. In the GEE model, all groups had higher sedation levels than the saline only group (P < 0.001). None of the protocols had a significant effect on sedation levels compared to the tramadol group.

Conclusion: The combined administration of naloxone and diazepam in acute-on-chronic tramadol poisoning can effectively reduce most seizure variables compared to tramadol use alone. However, none of the treatments improved sedation levels.

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来源期刊
Behavioral and Brain Functions
Behavioral and Brain Functions 医学-行为科学
CiteScore
5.90
自引率
0.00%
发文量
11
审稿时长
6-12 weeks
期刊介绍: A well-established journal in the field of behavioral and cognitive neuroscience, Behavioral and Brain Functions welcomes manuscripts which provide insight into the neurobiological mechanisms underlying behavior and brain function, or dysfunction. The journal gives priority to manuscripts that combine both neurobiology and behavior in a non-clinical manner.
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