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抗癫痫药物的神经保护作用。

Neuroprotective effects of antiepileptic drugs.

作者信息

Trojnar Michał K, Małek Robert, Chrościńska Magdalena, Nowak Stanisław, Błaszczyk Barbara, Czuczwar Stanisław J

机构信息

Department of Pathophysiology, Medical University, Jaczewskiego 8, PL 20-090 Lublin, Poland.

出版信息

Pol J Pharmacol. 2002 Nov-Dec;54(6):557-66.

Abstract

Experimental and clinical data indicate that epilepsy and seizures lead to neuronal cell loss and irreversible brain damage. This neurodegeneration results not only in the central nervous system dysfunction but may also be responsible for the decreased efficacy of some antiepileptic drugs (AEDs). The aim of this review was to assemble current literature data on neuroprotective properties of AEDs. The list of hypothetical neuroprotectants is long and consists of substances which act via different mechanisms. We focus on AEDs since this heterogeneous group of pharmaceuticals, as far as mechanisms of their action and mechanisms of neuronal death are concerned, should provide protection in addition to antiseizure effect itself. Most studies on neuroprotection are based on animal experimental models of neuronal degeneration. Electrically and pharmacologically evoked seizures as well as different models of ischemia are frequently used. Although our knowledge about properties of AEDs is still not complete and discrepancies occasionally occur, the group seems to be promising in terms of neuroprotection. Some of the drugs, though, turn out to be neutral or even have adverse effects on the central nervous system, especially on immature brain tissue (barbiturates and benzodiazepines). Unfortunatelly, we cannot fully extrapolate animal data to humans, therefore further well designed clinical trials are necessary to determine neuroprotective properties of AEDs in humans. However, there is a hope that AEDs will have a potential to serve as neuroprotectants not only in seizures, but perhaps, in other neurodegenerative conditions in humans as well. The novel AEDs (especially lamotrigine, tiagabine, and topiramate) seem particularly promising.

摘要

实验和临床数据表明,癫痫和癫痫发作会导致神经元细胞丧失和不可逆的脑损伤。这种神经退行性变不仅会导致中枢神经系统功能障碍,还可能是某些抗癫痫药物(AEDs)疗效降低的原因。本综述的目的是汇总有关AEDs神经保护特性的当前文献数据。假设的神经保护剂列表很长,包括通过不同机制起作用的物质。我们关注AEDs,因为就其作用机制和神经元死亡机制而言,这类异质性药物除了抗癫痫作用本身外,还应提供保护作用。大多数关于神经保护的研究基于神经元变性的动物实验模型。经常使用电刺激和药物诱发的癫痫发作以及不同的缺血模型。尽管我们对AEDs特性的了解仍不完整,偶尔会出现差异,但就神经保护而言,这类药物似乎很有前景。然而,有些药物对中枢神经系统,尤其是对未成熟脑组织(巴比妥类药物和苯二氮䓬类药物)是中性的,甚至有不良影响。不幸的是,我们无法将动物数据完全外推至人类,因此需要进一步设计良好的临床试验来确定AEDs在人类中的神经保护特性。然而,有希望的是,AEDs不仅在癫痫发作中,而且可能在人类其他神经退行性疾病中也有作为神经保护剂的潜力。新型AEDs(尤其是拉莫三嗪、噻加宾和托吡酯)似乎特别有前景。

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