Gean P W, Huang C C, Kuo J R, Lin J H, Yi P L, Tsai J J
Department of Pharmacology, College of Medicine, National Cheng-Kung University Tainan City, Taiwan, Republic of China.
Chin J Physiol. 1993;36(4):199-204.
The mechanism of action of the anticonvulsant drug carbamazepine was studied in rat hippocampal and amygdaloid slices using intracellular recording techniques. Stimulation of the Schaffer collateral/commissural pathway evoked an excitatory postsynaptic potential (EPSP) in CA1 pyramidal cells. Thirty minutes after superfusing with Mg(++)-free solution, the same stimulus intensity triggered burst firing. Application of carbamazepine reversibly reduced the burst duration in a dose-dependent manner. Synaptic response mediated by the N-methyl-D-aspartate (NMDA) receptors (EPSPNMDA) was isolated pharmacologically by application of a solution containing non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX,10 microM) and gamma-aminobutyric acidA receptor or antagonist picrotoxin (50 microM). Carbamazepine reversibly blocked the amplitude of EPSPNMDA in a concentration which did not affect the normal synaptic transmission. These results suggest that the combined blockade of NMDA receptors and firing of action potential forms the basis for the anticonvulsant effect of carbamazepine.
采用细胞内记录技术，在大鼠海马和杏仁核切片中研究了抗惊厥药物卡马西平的作用机制。刺激Schaffer侧支/联合通路可在CA1锥体细胞中诱发兴奋性突触后电位（EPSP）。用无镁溶液灌流30分钟后，相同的刺激强度引发爆发性放电。应用卡马西平以剂量依赖的方式可逆地缩短爆发持续时间。通过应用含有非NMDA受体拮抗剂6-氰基-7-硝基喹喔啉-2,3-二酮（CNQX，10μM）和γ-氨基丁酸A受体拮抗剂印防己毒素（50μM）的溶液，从药理学上分离出由N-甲基-D-天冬氨酸（NMDA）受体介导的突触反应（EPSPNMDA）。卡马西平在不影响正常突触传递的浓度下可逆地阻断EPSPNMDA的幅度。这些结果表明，NMDA受体的联合阻断和动作电位的发放构成了卡马西平抗惊厥作用的基础。
