Löscher W, Rundfeldt C, Hönack D
Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Hannover, Germany.
Eur J Neurosci. 1993 Nov 1;5(11):1545-50. doi: 10.1111/j.1460-9568.1993.tb00224.x.
Excitatory amino acid transmitters are involved in the initiation of seizures and their propagation. Most attention has been directed to synapses using N-methyl-D-aspartate (NMDA) receptors, although more recent evidence indicates potential roles for the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors as well. In the present experiments in amygdala-kindled rats, i.e. a model of partial epilepsy, competitive and uncompetitive NMDA antagonists exerted only weak anticonvulsant effects, whereas the AMPA antagonist 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)quinoxaline (NBQX) potently increased focal seizure threshold and inhibited seizure spread from the focus. These effects of NBQX were dramatically increased by pretreatment with low doses of NMDA antagonists, whereas adverse effects of NBQX were not potentiated. These data suggest that both non-NMDA and NMDA receptors are critically involved in the kindled state, and that combinations of AMPA and NMDA receptor antagonists provide a new strategy for treatment of epileptic seizures.
兴奋性氨基酸递质参与癫痫发作的起始及其传播。尽管最近有证据表明α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体也有潜在作用，但大多数研究都集中在使用N-甲基-D-天冬氨酸（NMDA）受体的突触上。在目前对杏仁核点燃大鼠（即部分癫痫模型）的实验中，竞争性和非竞争性NMDA拮抗剂仅发挥微弱的抗惊厥作用，而AMPA拮抗剂2,3-二羟基-6-硝基-7-氨磺酰基苯并（F）喹喔啉（NBQX）能显著提高局灶性癫痫发作阈值并抑制癫痫发作从病灶处扩散。低剂量NMDA拮抗剂预处理可显著增强NBQX的这些作用，而NBQX的不良反应并未增强。这些数据表明，非NMDA和NMDA受体都与点燃状态密切相关，并且AMPA和NMDA受体拮抗剂的联合使用为癫痫发作的治疗提供了一种新策略。
