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吡唑衍生物的抗惊厥药理活性:治疗癫痫的潜在益处。

Pharmacological Activity of Pyrazole Derivatives as an Anticonvulsant for Benefit against Epilepsy.

机构信息

Department of Child Healthcare, Shandong Provincial Third Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Innoscience Research Sdn Bhd, Subang Jaya, Malaysia.

出版信息

Neuroimmunomodulation. 2021;28(2):90-98. doi: 10.1159/000513297. Epub 2021 Mar 26.

Abstract

INTRODUCTION

Pediatric patients with epilepsy are prone to cognitive impairments during growth and long-term use of most antiepileptic drugs (AED). The affected children do not respond to conventional AED and may require novel drugs to manage the disease. Valproic acid, a first-line drug to treat epilepsy, is associated with serious side effects, which precludes its wider use. Thus, in the present study, we intended to develop novel substituted pyrazoles.

METHODS

The molecules were tested for anticonvulsive activity in Swiss albino mice via maximal electroshock seizure and subcutaneous pentylenetetrazole assays. The most potent molecule among the class was further assayed for its effect on behavioral and CNS depressant activity. The effect of the most potent compounds was also analyzed on various indices of oxidative stress and inflammation in mice.

RESULTS

The designed compounds showed significant anticonvulsive activity in mice revealing 7h as the most potent anticonvulsive agent. The most potent anticonvulsant molecule 7h further showed no behavioral alteration and considerable CNS depressant activity. It also reduces the level of oxidative stress and inflammation in the mice.

CONCLUSION

Our study demonstrated utility of pyrazole derivatives as anticonvulsants against epilepsy.

摘要

简介

儿科癫痫患者在成长过程中容易出现认知障碍,而且大多数抗癫痫药物(AED)长期使用也会出现这种情况。受影响的儿童对常规 AED 反应不佳,可能需要新型药物来治疗疾病。丙戊酸是治疗癫痫的一线药物,但它会产生严重的副作用,限制了其更广泛的应用。因此,在本研究中,我们旨在开发新型取代的吡唑类化合物。

方法

通过最大电休克惊厥和皮下戊四氮试验,在瑞士白化小鼠中测试这些分子的抗惊厥活性。在该类化合物中,最有效的分子进一步用于检测其对行为和中枢神经系统抑制活性的影响。还分析了最有效的化合物对小鼠各种氧化应激和炎症指标的影响。

结果

设计的化合物在小鼠中表现出显著的抗惊厥活性,表明 7h 是最有效的抗惊厥剂。最有效的抗惊厥分子 7h 进一步显示没有行为改变和相当大的中枢神经系统抑制活性。它还降低了小鼠的氧化应激和炎症水平。

结论

我们的研究表明,吡唑衍生物作为抗癫痫药物具有一定的应用价值。

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