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格列本脲对小鼠实验性诱发癫痫活动的逆转作用。

Reversal of experimentally induced seizure activity in mice by glibenclamide.

作者信息

Pithadia Anand B, Navale Archana, Mansuri Javed, Shetty Rajesh S, Panchal Shital, Goswami Sunita

机构信息

Department of Pharmacology, Parul Institute of Pharmacy, Vadodara.

Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad.

出版信息

Ann Neurosci. 2013 Jan;20(1):10-2. doi: 10.5214/ans.0972.7531.200105.

Abstract

BACKGROUND

ATP sensitive potassium channels are widely distributed in central nervous system (CNS) and these channels could be the target in CNS disorders by their modulators.

PURPOSE

The present study was designed to investigate the anticonvulsant potential of glibenclamide on MES induced seizure and pentylenetetrazole induced seizure in mice.

METHODS

Seizures were induced in 7 months albino mice with a single 12 mA intensity of 50 Hz stimulus for 0.2 s using electroconvulsiometer. Tonic flexion, tonic extension, clonic convulsion and mortality protection were recorded, 60 minutes after the oral administration of the vehicle (3% Tween 80), Standard (diazepam 3 mg/kg i.p.) and glibenclamide (5 mg/kg). In second model, seizures were induced with a single convulsive dose (80 mg/kg i.p) of pentylentetrazole (PTZ). Seizures were assessed in terms of onset of seizure, number of jerks, onset of tonic convulsion and clonic convulsions and mortality protection. The study was performed at antidiabetic dose of glibenclamide 5 mg/kg per oral.

RESULTS

Glibenclamide (5 mg/kg p.o.) showed significant (p<0.05) protective activity in MES induced seizures and attenuated pentylenetetrazole-induced seizure activity in mice. The anticonvulsant action of glibenclamide was noticeable in this study. However, further studies are required to elucidate its full anticonvulsant potential.

CONCLUSIONS

Glibenclamide is able to exert protective effects in MES induced seizures and attenuates pentylenetetrazole induced seizure activity in mice.

摘要

背景

ATP敏感性钾通道广泛分布于中枢神经系统(CNS),其调节剂可作用于这些通道,使其成为中枢神经系统疾病的治疗靶点。

目的

本研究旨在探讨格列本脲对小鼠最大电休克(MES)诱导的癫痫发作和戊四氮诱导的癫痫发作的抗惊厥作用。

方法

使用电惊厥仪,以50Hz的频率、12mA的强度对7月龄白化病小鼠进行单次0.2秒的刺激,诱导癫痫发作。在口服赋形剂(3%吐温80)、标准药物(地西泮3mg/kg腹腔注射)和格列本脲(5mg/kg)60分钟后,记录强直性屈曲、强直性伸展、阵挛性惊厥和死亡保护情况。在第二个模型中,用单次惊厥剂量(80mg/kg腹腔注射)的戊四氮(PTZ)诱导癫痫发作。根据癫痫发作的起始时间、抽搐次数、强直性惊厥和阵挛性惊厥的起始时间以及死亡保护情况评估癫痫发作。本研究以格列本脲抗糖尿病剂量5mg/kg口服进行。

结果

格列本脲(5mg/kg口服)在MES诱导的癫痫发作中显示出显著(p<0.05)的保护活性,并减轻了小鼠戊四氮诱导的癫痫发作活性。在本研究中,格列本脲的抗惊厥作用显著。然而,需要进一步研究以阐明其全部抗惊厥潜力。

结论

格列本脲能够对MES诱导的癫痫发作发挥保护作用,并减轻小鼠戊四氮诱导的癫痫发作活性。

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Potassium channels as targets for therapeutic intervention.作为治疗干预靶点的钾通道
Sci STKE. 2005 Sep 20;2005(302):pe46. doi: 10.1126/stke.stke.3022005pe46.

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