Anti-seizure medications and estradiol for neuroprotection in epilepsy: the 2013 update.
Anti-seizure medications and estradiol for neuroprotection in epilepsy: the 2013 update.
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DOI：
10.2174/1574889811308010004
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发表时间：
2013-03
期刊：
影响因子：
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通讯作者：
L. Velíšek;N. Nebieridze;T. Chachua;J. Velíšková
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文献类型：
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作者：
L. Velíšek;N. Nebieridze;T. Chachua;J. Velíšková
目前的癫痫治疗仍然是有症状的使用抗癫痫药物，而不是抗癫痫药物。这种疗法可以控制癫痫发作的活动，但不能预防甚至治愈癫痫。可能干扰导致癫痫(癫痫发生)的过程的治疗策略将比目前的方法有很大的好处。神经元损伤导致神经元网络重塑(如在颞叶癫痫时在海马区)，是持续癫痫发生的重要组成部分之一。因此，减轻癫痫引起的神经元损伤和网络重组的治疗策略可能成为对抗癫痫形成恶化过程的有力工具。目前的抗癫痫药物，特别是丙戊酸，具有一定的神经保护潜力。同样，有一些新的抗癫痫药物，如瑞格他滨和左乙拉西坦，也有一些神经保护的希望。然而，抗癫痫药物的神经保护潜力往往很弱，或者被与长期治疗相关的负面副作用所掩盖，因此超过了益处。因此，人们的注意力转移到了已经确定的具有神经保护潜力的不同化合物上。在正在研究的类固醇激素中，有两组似乎很有趣：β-雌二醇组和选择性雌激素受体调节剂-SERM组。在低剂量下，β-雌二醇对神经退行性疾病具有神经保护作用。然而，它在癫痫诱导的神经保护中的应用被人们对雌激素促惊厥特性的普遍看法所混淆。在这里，我们回顾了这两个特征，对神经元兴奋性和神经保护的影响，在特定条件下适用，并可通过考虑受试者的剂量范例、时间、性别和年龄以及他们的性腺激素状况(包括黄体酮：对立与非对立雌激素)的个体化治疗来区分。多项研究表明，β-雌二醇确实具有保护神经元免受癫痫所致损伤的效力。需要进一步的研究来确定β-雌二醇和SERM在癫痫诱导的神经保护中的确切机制，以实现真正的个体化和有效的治疗。本文介绍了一些有前景的抗癫痫药物专利。
Current epilepsy therapy is still symptomatic using anti-seizure, rather than anti-epileptic, medications. This therapy may control the seizure activity but does not prevent or even cure epilepsy. Treatment strategies that could interfere with the process leading to epilepsy (epileptogenesis) would have significant benefits over the current approaches. Neuronal damage contributing to remodeling of the neuronal networks (such as in the hippocampus during temporal lobe epilepsy) is one of the significant components of ongoing epileptogenesis. Thus, treatment strategies alleviating seizure-induced neuronal damage and network reorganization may become powerful tools fighting the deteriorating process of epileptogenesis. Current anti-seizure medications, especially valproic acid, have some neuroprotective potential. Similarly, there is some hope of neuroprotection with newer anti-seizure drugs such as retigabine and levetiracetam. However, the neuroprotective potential of anti-seizure medications is frequently weak or masked by negative side effects associated with long-term treatment, therefore exceeding the benefits.. Thus, the attention is shifted to different compounds with already established neuroprotective potential. Among steroid hormones under investigation, two groups appear interesting: β-estradiol and selective estrogen receptor modulators - SERM. In low doses, β-estradiol has neuroprotective potency in neurodegenerative diseases. However, its use for seizure-induced neuroprotection is confounded by a common perception of proconvulsant features of estrogens. Here we review that both features, effects on neuronal excitability and neuroprotection, apply under specific conditions and may be separated by individualized therapy taking into account the dosage paradigm, timing, sex and age of the subjects and their gonadal hormone status (including progesterone: opposed vs. unopposed estrogen). Several studies have demonstrated that β-estradiol has indeed potency to protect neurons from seizure-induced damage. Additional studies are required to determine exact mechanisms of β-estradiol and SERMs in seizure-induced neuroprotection for truly individualized and effective therapy. The article presents some promising patents on anti-seizure medications.