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苏黎世新型抗癫痫药物共识会议。引言:目标。

Zurich Consensus Conference on New Antiepileptic Drugs. Introduction: goals.

作者信息

Wieser H G

机构信息

Department of Neurology, University Hospital Zürich, Switzerland.

出版信息

Epilepsia. 1994;35 Suppl 5:S1-5. doi: 10.1111/j.1528-1157.1994.tb05958.x.

Abstract

Epilepsy is characterized by recurrent seizures. Many epilepsies with focal seizures as well as convulsive generalized seizures respond satisfactorily to antiepileptic drugs (AEDs) that reduce repetitive firing (e.g., phenytoin, carbamazepine, and valproate) or that augment GABAA-mediated inhibition (e.g., phenobarbital and benzodiazepines). A number of drugs presently under development, such as NMDA receptor antagonists, loreclezole, losigamone, methysticine, and dextromethorphan, are promising in acute animal models of otherwise drug-resistant convulsant activity. As a result of recent studies in both experimental models and surgically resected human epileptic brain, the prospects for development of AEDs have significantly improved. Several new AEDs recently have reached the commercial market or are in experimental or clinical trials. A comparative presentation of the standing of the new AEDs with respect to their efficacy and side effects is necessary, but still very difficult. Because initial experience with new AEDs is restricted to populations with severe drug-resistant epilepsy, the crucial question whether potential new AEDs can alter prognosis is not yet definitively answered. There is a clear need to compare the effects of standard AEDs and new AEDs in naive patients and over longer follow-up periods. Moreover, because of the strong desire to develop antiepileptic therapy that directly treats the primary etiology of a given epileptic syndrome, or modifies the neurobiological processes that cause recurrent seizures, better experimental epilepsy models for chronic epilepsy and further clinical studies are necessary to increase the knowledge on the pathophysiology of distinct epileptic syndromes. In this respect, studies on the differences between responders and nonresponders to a given AED treatment are extremely valuable.

摘要

癫痫的特征是反复发作。许多伴有局灶性发作以及惊厥性全面性发作的癫痫,对抗癫痫药物(AEDs)反应良好,这些药物可减少重复放电(如苯妥英、卡马西平和丙戊酸盐)或增强GABAA介导的抑制作用(如苯巴比妥和苯二氮䓬类药物)。目前正在研发的一些药物,如NMDA受体拮抗剂、氯雷唑、洛西加莫、甲基丁香酚和右美沙芬,在原本耐药的惊厥活性急性动物模型中显示出前景。由于最近在实验模型和手术切除的人类癫痫脑中的研究,AEDs的研发前景有了显著改善。几种新的AEDs最近已进入商业市场或正处于实验或临床试验阶段。对新AEDs的疗效和副作用进行比较介绍是必要的,但仍然非常困难。因为对新AEDs的初步经验仅限于严重耐药性癫痫患者群体,潜在的新AEDs是否能改变预后这一关键问题尚未得到明确解答。显然需要比较标准AEDs和新AEDs在初治患者以及更长随访期内的效果。此外,由于迫切希望开发能直接治疗特定癫痫综合征原发性病因或改变导致反复发作的神经生物学过程的抗癫痫疗法,需要更好的慢性癫痫实验模型和进一步的临床研究,以增加对不同癫痫综合征病理生理学的认识。在这方面,对特定AED治疗的反应者和无反应者之间差异的研究极具价值。

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