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. 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. 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. 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.

中文翻译：

---

纳洛酮、地西泮和槲皮素对慢性曲马多给药急性发作和镇静的影响：一项实验研究

曲马多是一种广泛使用的合成阿片类药物。大量研究以前集中在这种药物的神经学作用上，而各种治疗减少相关副作用的功效尚未得到很好的研究。本研究旨在评估纳洛酮、地西泮和槲皮素对雄性大鼠曲马多过量引起的癫痫发作和镇静水平的保护作用。该项目是用 72 只平均体重为 200-250 克的雄性 Wistar 大鼠进行的。大鼠被随机分配到八组。曲马多以 25 mg/kg/天的初始剂量腹膜内给药。第 14 天，曲马多以 75 mg/kg 的剂量单独或与纳洛酮、地西泮和槲皮素（急性和慢性）一起单独或联合注射。最后一天监测大鼠6 h，观察数量、持续时间、在 6 小时的观察期内测量癫痫发作的严重程度（使用拉辛标准）。镇静水平也基于 0 到 3 的 4 点标准进行评估。使用 Kruskal-Wallis、卡方、回归分析和广义估计方程 (GEE) 检验在 SPSS 软件中分析数据。显着性水平设定为 P < 0.05。与单独使用曲马多相比，纳洛酮-地西泮组合减少了癫痫发作的次数、严重程度和累积持续时间，并且与其他治疗相比，在更大程度上减少了高强度癫痫发作的次数（3、4 级）。单独使用纳洛酮可减少癫痫发作的次数和持续时间，但会增加轻度癫痫发作的次数（2 级）。地西泮降低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）。与单独使用曲马多组相比，急性槲皮素组的轻度（2 级）和中度（3 级）癫痫发作次数较多。慢性槲皮素给药显着增加轻度癫痫发作的次数。在 GEE 模型中，所有组的镇静水平均高于仅盐水组（P < 0.001）。与曲马多组相比，没有一个方案对镇静水平有显着影响。与单独使用曲马多相比，在慢加急性曲马多中毒中联合使用纳洛酮和地西泮可以有效减少大多数癫痫发作变量。然而，没有一种治疗能改善镇静水平。慢性槲皮素给药显着增加轻度癫痫发作的次数。在 GEE 模型中，所有组的镇静水平均高于仅盐水组（P < 0.001）。与曲马多组相比，没有一个方案对镇静水平有显着影响。与单独使用曲马多相比，在慢加急性曲马多中毒中联合使用纳洛酮和地西泮可以有效减少大多数癫痫发作变量。然而，没有一种治疗能改善镇静水平。慢性槲皮素给药显着增加轻度癫痫发作的次数。在 GEE 模型中，所有组的镇静水平均高于仅盐水组（P < 0.001）。与曲马多组相比，没有一个方案对镇静水平有显着影响。与单独使用曲马多相比，在慢加急性曲马多中毒中联合使用纳洛酮和地西泮可以有效减少大多数癫痫发作变量。然而，没有一种治疗能改善镇静水平。与单独使用曲马多相比，在慢加急性曲马多中毒中联合使用纳洛酮和地西泮可以有效减少大多数癫痫发作变量。然而，没有一种治疗能改善镇静水平。与单独使用曲马多相比，在慢加急性曲马多中毒中联合使用纳洛酮和地西泮可以有效减少大多数癫痫发作变量。然而，没有一种治疗能改善镇静水平。