Calabresi P, Siniscalchi A, Pisani A, Stefani A, Mercuri N B, Bernardi G
Clinica Neurologica, Università di Roma Tor Vergata, Italy.
Neurology. 1996 Aug;47(2):557-62. doi: 10.1212/wnl.47.2.557.
We studied the action of the new antiepileptic drugs lamotrigine (LTG), GP 47779 (the active metabolite of oxcarbazepine), and felbamate (FBM) on stimulus-evoked field potentials recorded from rat prefrontal and frontal cortical slices. In the presence of physiologic concentrations of extracellular magnesium (1.2 mM) the field potential amplitude was not affected by the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, 2-amino-5-phosphonovalerate (APV), while it was blocked by the non-NMDA glutamate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). When magnesium was removed from the bathing medium, there was a significant NMDA-mediated component of the field potential. LTG and GP 47779 decreased, in a dose-dependent manner, the field potential amplitude under both experimental conditions. FBM caused a dose-related decrease of the field potential amplitude only in the absence of external magnesium, suggesting a selective interaction with an NMDA-mediated component of this potential. These findings indicate that the reduction of cortical excitatory transmission might represent a common target for new antiepileptic drugs.
我们研究了新型抗癫痫药物拉莫三嗪（LTG）、GP 47779（奥卡西平的活性代谢产物）和非氨酯（FBM）对大鼠前额叶和额叶皮质切片记录的刺激诱发场电位的作用。在生理浓度的细胞外镁（1.2 mM）存在下，场电位幅度不受N-甲基-D-天冬氨酸（NMDA）谷氨酸受体拮抗剂2-氨基-5-磷酸戊酸（APV）的影响，而被非NMDA谷氨酸受体拮抗剂6-氰基-7-硝基喹喔啉-2,3-二酮（CNQX）阻断。当从灌流介质中去除镁时，场电位存在显著的NMDA介导成分。在两种实验条件下，LTG和GP 47779均以剂量依赖性方式降低场电位幅度。FBM仅在无细胞外镁的情况下导致场电位幅度呈剂量相关下降，提示其与该电位的NMDA介导成分存在选择性相互作用。这些发现表明，降低皮质兴奋性传递可能是新型抗癫痫药物的共同靶点。
