Pursuing paradoxical proconvulsant prophylaxis for epileptogenesis.
Pursuing paradoxical proconvulsant prophylaxis for epileptogenesis.
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DOI：
10.1111/j.1528-1167.2009.02173.x
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发表时间：
2009-07
期刊：
影响因子：
5.6
通讯作者：
Soltesz I
中科院分区：
文献类型：
--
作者：
Armstrong C;Morgan RJ;Soltesz I
对于任何后天性疾病，本质上有两种潜在的治疗选择：对症治疗或预防性治疗。对于各种不同的脑损伤后的获得性癫痫，仍然完全缺乏预防性治疗选择，同时这些癫痫一旦出现就对抗癫痫药物的对症治疗产生耐药性。然而，对于基础研究人员和临床医生来说，预防策略的制定在逻辑上都具有挑战性。尽管如此，大麻素靶向药物提供了一个非常有趣的例子，说明中枢神经系统内的系统可以对过度兴奋和癫痫发作产生非常不同的急性和长期影响。在这篇综述中，我们概述了大麻素的研究，表明虽然大麻素拮抗剂具有强烈的促惊厥作用，但它们可能对多种病因造成的脑损伤后的长期过度兴奋产生有益的影响，使它们成为进一步研究作为获得性癫痫预防药物的有希望的候选者。然后，我们讨论这一发现对未来预防性治疗尝试的一些影响，特别是，预防可能的时间非常短，传统抗惊厥药可能干扰预防策略的可能性，以及超越抗惊厥药（甚至促惊厥药）来寻找获得性癫痫的理想预防策略的重要性。
There are essentially two potential treatment options for any acquired disorder: symptomatic or prophylactic. For acquired epilepsies which follow a variety of different brain insults, there remains a complete lack of prophylactic treatment options while at the same time these epilepsies are notoriously resistant to symptomatic treatments with antiepileptic drugs once they have emerged. The development of prophylactic strategies is, however, logistically challenging, both for basic researchers and clinicians. Nevertheless, cannabinoid-targeting drugs provide a very interesting example of a system within the CNS that can have very different acute and long-term effects on hyperexcitability and seizures. In this review, we outline research on cannabinoids suggesting that while cannabinoid antagonists are acutely pro-convulsant, they may have beneficial effects on long-term hyperexcitability following brain insults of multiple etiologies, making them promising candidates for further investigation as prophylactics against acquired epilepsy. We then discuss some of the implications of this finding on future attempts at prophylactic treatments, specifically, the very short window within which prevention may be possible, the possibility that traditional anticonvulsants may interfere with prophylactic strategies, and the importance of moving beyond anticonvulsants—even to proconvulsants—to find the ideal preventative strategy for acquired epilepsy.
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影响因子：
82.9
作者：
Chen, K;Baram, TZ;Soltesz, I
通讯作者：
Soltesz, I
DOI：
10.1073/pnas.0409641102
发表时间：
2005-06-28
影响因子：
11.1
作者：
Bernard, C;Milh, M;Gozlan, H
通讯作者：
Gozlan, H
影响因子：
8.9
作者：
Annegers, JF;Rocca, WA;Hauser, WA
通讯作者：
Hauser, WA
影响因子：
3.6
作者：
Dudek, F Edward;Bertram, Edward H;Staley, Kevin J
通讯作者：
Staley, Kevin J
影响因子：
11
作者：
Appleton, RE;Demellweek, C
通讯作者：
Demellweek, C