Pursuing paradoxical proconvulsant prophylaxis for epileptogenesis

被引:29
作者
Armstrong, Caren [1 ]
Morgan, Robert J. [1 ]
Soltesz, Ivan [1 ]
机构
[1] Univ Calif Irvine, Dept Anat & Neurobiol, Irvine, CA 92697 USA
基金
美国国家卫生研究院;
关键词
Epilepsy; Endocannabinoids; Epileptogenesis; Cannabinoid type 1; SR141716A; CANNABINOID RECEPTOR ANTAGONIST; RANDOMIZED CONTROLLED-TRIAL; PROLONGED FEBRILE SEIZURES; TEMPORAL-LOBE EPILEPSY; POSTTRAUMATIC EPILEPSY; ENDOCANNABINOID SYSTEM; LONG-TERM; STATUS EPILEPTICUS; HEAD-INJURY; SR; 141716A;
D O I
10.1111/j.1528-1167.2009.02173.x
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
P>There are essentially two potential treatment options for any acquired disorder: symptomatic or prophylactic. For acquired epilepsies that follow a variety of different brain insults, there remains a complete lack of prophylactic treatment options, whereas at the same time these epilepsies are notoriously resistant, once they have emerged, to symptomatic treatments with antiepileptic drugs. The development of prophylactic strategies is logistically challenging, both for basic researchers and clinicians. Nevertheless, cannabinoid-targeting drugs provide a very interesting example of a system within the central nervous system (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 although cannabinoid antagonists are acutely proconvulsant, 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.
引用
收藏
页码:1657 / 1669
页数:13
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