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递增电流电击惊厥试验:一种评估药物对小鼠抗惊厥和促惊厥活性的新方法。

Increasing-current electroshock seizure test: a new method for assessment of anti- and pro-convulsant activities of drugs in mice.

作者信息

Kitano Y, Usui C, Takasuna K, Hirohashi M, Nomura M

机构信息

Drug Safety Research Center, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.

出版信息

J Pharmacol Toxicol Methods. 1996 Feb;35(1):25-9. doi: 10.1016/1056-8719(95)00115-8.

DOI:10.1016/1056-8719(95)00115-8
PMID:8645877
Abstract

We developed the increasing-current electroshock seizure (ICES) test, a new method for assessment of anti- and pro-convulsant activities of drugs in mice. In this method, a single train of pulses (square wave, 5 msec, 20 Hz) of linearly increasing intensity from 5 to 30 mA (increment of 0.1 mA/0.1 sec, i.e., 5-30 mA in 25 sec) was applied via ear electrodes. The current at which tonic hindlimb extension occurred was recorded as the seizure threshold. Thus, this method allows determination of the seizure threshold current for individual animals. Carbamazepine, phenytoin, valproate, phenobarbital, diazepam, and morphine all increased the seizure threshold current in a dose-dependent manner, whereas ethosuximide was not effective. The seizure threshold current decreased after treatment with reserpine, chlorpromazine, aminophylline, strychnine, pentylenetetrazol, bicuculline, picrotoxin, and ethyl-beta-carboline-3-carboxylate (beta-CCE). These results indicate that the ICES test, like the maximal electroshock seizure test, is a model of grand mal-type seizure and is useful for evaluation of both the anti- and pro-convulsant activities of drugs.

摘要

我们开发了递增电流电击惊厥(ICES)试验,这是一种评估小鼠药物抗惊厥和促惊厥活性的新方法。在该方法中,通过耳部电极施加一系列强度从5到30 mA线性增加(以0.1 mA/0.1秒的增量,即25秒内从5到30 mA)的单脉冲序列(方波,5毫秒,20赫兹)。将出现强直性后肢伸展时的电流记录为惊厥阈值。因此,该方法可以确定个体动物的惊厥阈值电流。卡马西平、苯妥英、丙戊酸、苯巴比妥、地西泮和吗啡均以剂量依赖性方式增加惊厥阈值电流,而乙琥胺无效。用利血平、氯丙嗪、氨茶碱、士的宁、戊四氮、荷包牡丹碱、印防己毒素和β-咔啉-3-羧酸乙酯(β-CCE)处理后惊厥阈值电流降低。这些结果表明,ICES试验与最大电击惊厥试验一样,是大发作型惊厥的模型,可用于评估药物的抗惊厥和促惊厥活性。

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