Armand V, Rundfeldt C, Heinemann U
Department of Neurophysiology, Institute of Physiology, Universitätsklinikum Charité, Humboldt University Berlin, Germany.
Epilepsia. 2000 Jan;41(1):28-33. doi: 10.1111/j.1528-1157.2000.tb01501.x.
The objective of this study was to evaluate the effect of a new antiseizure drug, retigabine (D-23129; N-(2-amino-4-[fluorobenzylamino]-phenyl) carbamic acid ethyl ester) on low-Mg2+-induced epileptiform discharges in rat in vitro.
Three types of epileptiform discharges (recurrent short discharges in the hippocampus, seizure-like events, and late recurrent discharges in the entorhinal cortex) were elicited in rat combined entorhinal cortex-hippocampal slices by perfusion with low-Mg2+-artificial cerebrospinal fluid (ACSF). The antiepileptic properties of retigabine were evaluated as effect on the frequency and amplitude of the epileptiform activities as well as time of onset of the effect in the entorhinal cortex (EC) and in hippocampal area CA1 (CA1) by using extracellular recording techniques.
Retigabine (20 microM) reversibly suppressed the recurrent short discharges otherwise sensitive only to high doses of valproate (VPA) but insensitive to standard antiepileptic drugs (AEDs) in CA1, whereas 10 microM reduced the frequency of discharges by 34+/-18.8%, with no significant effect on the amplitude. In EC, retigabine (50 microM) reversibly suppressed the seizure-like events, whereas 20 microM blocked seizure-like events in 71.5% of the slices. The seizure-like events were also sensitive to standard AEDs. Late recurrent discharges in EC that are not blocked by standard AEDs were reversibly suppressed by retigabine (100 microM), whereas 50 microM reduced the frequency of the discharges by 94.4+/-7.7%, and 20 microM, by 74.2+/-18.0%, with no significant effect on the amplitude.
Retigabine is an effective AED with suppressive effects on recurrent short discharges and on late recurrent discharges normally insensitive to standard AEDs.
本研究的目的是评估一种新型抗癫痫药物瑞替加滨（D - 23129；N - (2 - 氨基 - 4 - [氟苄基氨基] - 苯基) 氨基甲酸乙酯）对体外培养的大鼠低镁离子诱导的癫痫样放电的影响。
通过用低镁离子人工脑脊液（ACSF）灌注大鼠内嗅皮质 - 海马联合切片，诱发三种类型的癫痫样放电（海马中的反复短放电、癫痫样事件以及内嗅皮质中的晚期反复放电）。采用细胞外记录技术，评估瑞替加滨的抗癫痫特性，包括其对内嗅皮质（EC）和海马CA1区（CA1）癫痫样活动的频率、幅度以及起效时间的影响。
瑞替加滨（20 μM）可逆性抑制CA1区中原本仅对高剂量丙戊酸（VPA）敏感而对标准抗癫痫药物（AEDs）不敏感的反复短放电，而10 μM使放电频率降低34±18.8%，对幅度无显著影响。在EC中，瑞替加滨（50 μM）可逆性抑制癫痫样事件，而20 μM在71.5%的切片中阻断癫痫样事件。癫痫样事件也对标准AEDs敏感。EC中未被标准AEDs阻断的晚期反复放电被瑞替加滨（100 μM）可逆性抑制，而50 μM使放电频率降低94.4±7.7%，20 μM使放电频率降低74.2±18.0%，对幅度无显著影响。
瑞替加滨是一种有效的抗癫痫药物，对反复短放电和通常对标准AEDs不敏感的晚期反复放电具有抑制作用。
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