Giardina William J, Gasior Maciej
Abbott Laboratories, Abbott Park, Illinois, USA.
Curr Protoc Pharmacol. 2009 Jun;Chapter 5:Unit 5.22. doi: 10.1002/0471141755.ph0522s45.
Epilepsy is a common (50 million patients worldwide) neurological disorder characterized by seizures that are caused by episodic abnormal electrical activity in the brain. Animal models play an essential role in epilepsy research including the discovery and development of new antiepileptic drugs. Described in this unit are protocols for traditional acute tests in which seizures are induced by either an electrical stimulation or a convulsant agent in non-epileptic mice. Specifically, protocols for the following acute seizure tests are provided: the maximal electroshock induced test (MES), the maximal electroshock seizure threshold (MEST) test, the 6-Hz seizure test, the subcutaneous pentylenetetrazol (s.c. PTZ) seizure test, and the intravenous pentylenetetrazol (i.v. PTZ) seizure test. These tests can be used to characterize anticonvulsant and/or proconvulsant properties of compounds in mice. The MES, s.c. PTZ, and 6-Hz seizure tests represent the three most widely used animal tests in drug-screening programs. Although the parameters of these tests are optimized for mice, the same tests (except for the 6-Hz seizure test), with some modifications, can be used with rats.
癫痫是一种常见的(全球有5000万患者)神经系统疾病,其特征是由大脑中突发性异常电活动引起的癫痫发作。动物模型在癫痫研究中发挥着重要作用,包括新抗癫痫药物的发现和开发。本单元描述了传统急性试验的方案,即在非癫痫小鼠中通过电刺激或惊厥剂诱导癫痫发作。具体来说,提供了以下急性癫痫发作试验的方案:最大电休克诱导试验(MES)、最大电休克癫痫阈值(MEST)试验、6赫兹癫痫试验、皮下注射戊四氮(s.c.PTZ)癫痫试验和静脉注射戊四氮(i.v.PTZ)癫痫试验。这些试验可用于表征化合物在小鼠中的抗惊厥和/或促惊厥特性。MES、s.c.PTZ和6赫兹癫痫试验是药物筛选程序中使用最广泛的三种动物试验。尽管这些试验的参数是针对小鼠优化的,但相同的试验(6赫兹癫痫试验除外),经过一些修改后,也可用于大鼠。