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普瑞巴林、尼莫地平及其联合用药对抑制小鼠癫痫持续状态及预防死亡的作用。

Effects of Pregabalin, Nimodipine, and Their Combination in the Inhibition of Status Epilepticus and the Prevention of Death in Mice.

作者信息

Qureshi Itefaq, Riaz Azra, Khan Rafeeq, Baig Moona, Rajput Muhammad Ali

机构信息

University of Karachi, Department of Pharmacology, Karachi, Pakistan

Ziauddin University, Faculty of Pharmacy, Karachi, Pakistan

出版信息

Turk J Pharm Sci. 2021 Sep 1;18(4):398-404. doi: 10.4274/tjps.galenos.2020.95776.

Abstract

OBJECTIVES

The current study aims to evaluate the combined antiepileptic effects of pregabalin (PGB) and nimodipine (NMD) in an acute seizure model of epilepsy in mice.

MATERIALS AND METHODS

This study assessed the combined antiepileptic effects of PGB with NMD on death protection in mice. Pentylenetetrazole was used to induce seizures. Both drugs were used singly and in combination to judge anticonvulsant effects on an acute seizure model of epilepsy in mice. Diazepam (DZ) and valproate (VPT) were used as standard antiepileptic drugs.

RESULTS

The death protection in mice by both these drugs was observed in percentage and deliberated as marked change when the outcome of the tested drug was equal to ED of PGB and measured highly marked when the result was more than ED for PGB. Treatment with pregabalin and nimodipine combination revealed substantial mortality protection at 30+2.5 mg/kg dose and highly marked at doses from 35+5 mg/kg to 55+15 mg/kg, these effects were superior to individual effects of PGB, showing synergism, however lesser then classic drugs valproate and diazepam.

CONCLUSION

NMD showed synergistic anticonvulsant effect with PGB. However, clinical studies are required to establish the effectiveness of this combination in humans.

摘要

目的

本研究旨在评估普瑞巴林(PGB)和尼莫地平(NMD)在小鼠急性癫痫发作模型中的联合抗癫痫作用。

材料与方法

本研究评估了PGB与NMD联合对小鼠死亡保护的抗癫痫作用。用戊四氮诱导癫痫发作。两种药物单独使用及联合使用,以判断对小鼠急性癫痫发作模型的抗惊厥作用。地西泮(DZ)和丙戊酸盐(VPT)用作标准抗癫痫药物。

结果

观察到这两种药物对小鼠的死亡保护率,并在受试药物结果等于PGB的半数有效剂量(ED)时将其视为显著变化,当结果超过PGB的ED时则视为高度显著变化。普瑞巴林和尼莫地平联合治疗在30 + 2.5 mg/kg剂量时显示出显著的死亡率保护作用,在35 + 5 mg/kg至55 + 15 mg/kg剂量时作用高度显著,这些作用优于PGB的单独作用,表现出协同作用,然而低于经典药物丙戊酸盐和地西泮。

结论

NMD与PGB显示出协同抗惊厥作用。然而,需要进行临床研究以确定这种联合用药在人体中的有效性。

相似文献

本文引用的文献

1
The Role of Calcium Channels in Epilepsy.钙通道在癫痫中的作用。
Cold Spring Harb Perspect Med. 2016 Jan 4;6(1):a022723. doi: 10.1101/cshperspect.a022723.
2
Challenges in the clinical development of new antiepileptic drugs.新型抗癫痫药物临床研发中的挑战
Pharmacol Res. 2016 Jan;103:95-104. doi: 10.1016/j.phrs.2015.11.007. Epub 2015 Dec 2.
4
Epilepsy: new advances.癫痫:新进展。
Lancet. 2015 Mar 7;385(9971):884-98. doi: 10.1016/S0140-6736(14)60456-6. Epub 2014 Sep 24.
5
Animal models of epilepsy: use and limitations.癫痫动物模型:应用与局限性。
Neuropsychiatr Dis Treat. 2014 Sep 9;10:1693-705. doi: 10.2147/NDT.S50371. eCollection 2014.
7
T-type calcium channel blockers as neuroprotective agents.T型钙通道阻滞剂作为神经保护剂。
Pflugers Arch. 2014 Apr;466(4):757-65. doi: 10.1007/s00424-014-1454-x. Epub 2014 Feb 25.

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