Pugliese A M, Passani M B, Pepeu G, Corradetti R
Dipartimento di Farmacologia Preclinica e Clinica Mario Aiazzi-Mancini, Università di Firenze, Italy.
J Pharmacol Exp Ther. 1996 Dec;279(3):1100-8.
The antiepileptic drug felbamate (FBM) is known to block N-methyl-D-aspartate receptor-mediated responses and to decrease voltage-sensitive Na+ and Ca+2 channels. The present work was aimed at investigating the actions of FBM on synaptic potentials in the hippocampus, a region frequently involved in epileptic discharges. In rat hippocampal slices, application of FBM (100-1300 microM, 10 min) elicited a concentration-dependent, fully reversible decrease in amplitude of electrically evoked population spikes recorded extracellularly from the CA1 pyramidal cell layer. In intracellular recordings, FBM (50-300 microM) decreased the amplitude of excitatory postsynaptic potentials and reduced the probability of firing action potentials upon synaptic activation. Action potential frequency adaptation (accommodation), which typically limits repetitive firing in CA1 pyramidal cells, was increased. By using a paired-pulse protocol, FBM (300 microM) depressed the amplitude of paired excitatory postsynaptic potentials, without affecting the facilitation of the second response. In nominally Mg(+2)-free solution, FBM (100 microM) blocked N-methyl-D-aspartate receptor-mediated synaptic excitatory postsynaptic potentials isolated by the presence of 10 microM 6-nitro-7-sulfamoylbenzo(f)quinoxaline hydrochloride, a selective alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist, and 10 microM bicuculline or 25 microM picrotoxin. This effect was not reversed by the addition of 300 microM Gly. All these effects contribute to decrease excitatory synaptic transmission and are likely to limit neuron recruitment and propagation of epileptic discharges.
抗癫痫药物非氨酯（FBM）已知可阻断N-甲基-D-天冬氨酸受体介导的反应，并降低电压敏感性钠通道和钙通道。目前的研究旨在探讨FBM对海马体突触电位的作用，海马体是一个经常参与癫痫放电的区域。在大鼠海马体切片中，应用FBM（100 - 1300微摩尔，10分钟）可引起从CA1锥体细胞层细胞外记录的电诱发群体峰电位幅度呈浓度依赖性、完全可逆的降低。在细胞内记录中，FBM（50 - 300微摩尔）降低了兴奋性突触后电位的幅度，并降低了突触激活时产生动作电位的概率。动作电位频率适应性（适应）增加，这通常会限制CA1锥体细胞的重复放电。通过使用双脉冲方案，FBM（300微摩尔）抑制了双脉冲兴奋性突触后电位的幅度，但不影响第二个反应的易化。在名义上无镁离子的溶液中，FBM（100微摩尔）阻断了由10微摩尔盐酸6-硝基-7-氨磺酰基苯并[f]喹喔啉（一种选择性α-氨基-3-羟基-5-甲基异恶唑-4-丙酸受体拮抗剂）、10微摩尔荷包牡丹碱或25微摩尔印防己毒素分离出的N-甲基-D-天冬氨酸受体介导的突触兴奋性突触后电位。加入300微摩尔甘氨酸后，这种作用并未逆转。所有这些作用都有助于减少兴奋性突触传递，并可能限制神经元募集和癫痫放电的传播。
