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用于抗癫痫药物筛选的动物模型。

Animal models used in the screening of antiepileptic drugs.

作者信息

Kupferberg H

机构信息

National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892-9523, USA.

出版信息

Epilepsia. 2001;42 Suppl 4:7-12.

Abstract

The identification of potential therapeutic agents for the treatment of epilepsy requires the use of seizure models. These models can be either in vivo or in vitro, mechanism specific, mechanism independent, or seizure specific. To be predictive of therapeutic activity in patients, the models should approximate the events that precipitate seizures in humans. Model validation is defined by determining the pharmacologic characteristics using known clinically effective drugs. Mechanism-independent models were used to identify the first antiepileptic drugs [AEDs; e.g., phenobarbital (PB) and phenytoin (PHT)]. Mechanism-specific models are based on the fundamental process by which seizure propagation and inhibition occurs. Seizure-type models identify a compound's potential based on its effects on electrographic and behavioral response. No single model can be used to identify potential compounds adequately for development. The full pharmacologic-anticonvulsant profile of a potentially useful new therapeutic agent is required to ensure successful development.

摘要

确定用于治疗癫痫的潜在治疗药物需要使用癫痫发作模型。这些模型可以是体内模型或体外模型,机制特异性模型、机制非特异性模型或癫痫发作特异性模型。为了预测对患者的治疗活性,这些模型应近似于引发人类癫痫发作的事件。通过使用已知的临床有效药物确定药理学特征来定义模型验证。非特异性模型被用于确定首批抗癫痫药物(AEDs;例如苯巴比妥(PB)和苯妥英(PHT))。特异性模型基于癫痫发作传播和抑制发生的基本过程。癫痫发作类型模型根据化合物对脑电图和行为反应的影响来确定其潜力。没有单一模型能够充分用于确定有开发潜力的化合物。需要了解潜在有用的新治疗药物完整的抗惊厥药理学特征,以确保成功开发。

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