Effects of standard anticonvulsant drugs on different patterns of epileptiform discharges induced by 4-aminopyridine in combined entorhinal cortex-hippocampal slices
Effects of standard anticonvulsant drugs on different patterns of epileptiform discharges induced by 4-aminopyridine in combined entorhinal cortex-hippocampal slices
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DOI：
10.1016/s0006-8993(99)02348-3
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发表时间：
2000-03-17
期刊：
影响因子：
2.9
通讯作者：
Heinemann, U
中科院分区：
文献类型：
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作者：
Brückner, C;Heinemann, U
先前报道，应用 4-氨基吡啶 (4-AP) 会在内嗅皮质 (EC)-海马切片中产生不同模式的癫痫样放电：海马区 CA1 中的反复短放电 (RSD)、内侧内嗅皮质 (mEC) 中的癫痫样事件 (SLE) 和负向电位 (NGP)。利用场电位记录，我们研究了临床使用的标准抗惊厥药物苯妥英 (PHT)、卡马西平 (CBZ)、丙戊酸 (VPA) 和苯巴比妥 (PHB) 以及戊巴比妥 (PB) 对 4-AP 诱导的癫痫样活动的药理作用。抗惊厥药物表现出不同的效果：所有测试药物均能完全阻断 SLE。抑制所有癫痫样活动的丙戊酸似乎对 4-AP 诱导的活性具有所有药物中最基本的作用，因为在苯妥英和卡马西平的作用下，仍然可以观察到一些癫痫样活动。海马CA1区的RSD对不同的抗惊厥药没有反应。相反，PB 降低了 CA1 中 RSD 的频率，并提高了 EC 中 NGP 的频率。我们提出，4-AP 在联合内嗅皮质-海马切片中诱导的活性可能为开发针对难治性局灶性癫痫的新药提供体外模型。 (C) 2000 Elsevier Science B.V. 保留所有权利。
Application of 4-aminopyridine (4-AP) has previously been reported to produce different patterns of epileptiform discharges in entorhinal cortex (EC)-hippocampal slices: recurrent short discharges (RSDs) in hippocampal area CA1, seizure-like events (SLEs) and negative-going potentials (NGPs) in the medial entorhinal cortex (mEC). Using recordings of field potentials, we investigated the pharmacological effects of the clinically employed standard anticonvulsant drugs phenytoin (PHT), carbamazepine (CBZ), valproic acid (VPA) and phenobarbital (PHB) and those of pentobarbital (PB) on 4-AP-induced epileptiform activity. The anticonvulsant drugs showed different effects: SLEs were completely blocked by all tested drugs. Valproic acid, which suppressed all epileptiform activities, seemed to have the most fundamental effect of all drugs on 4-AP induced activity, because under phenytoin and carbamazepine, some epileptiform activity was still observable. The RSDs in hippocampal area CA1 of the hippocampus did not respond to the different anticonvulsants. In contrast, PB decreased the frequency of the RSDs in CA1 and enhanced the frequency of the NGPs in the EC. We propose that the activities induced by 4-AP in the combined entorhinal cortex-hippocampal slices may provide an in vitro model for the development of new drugs against difficult-to-treat focal epilepsy. (C) 2000 Elsevier Science B.V. All rights reserved.