Rogawski M A, Kurzman P S, Yamaguchi S I, Li H
Neuronal Excitability Section, Epilepsy Research Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 10 Center Drive Room 5N-250 MSC 1408, Bethesda, MD 20892-1408, USA.
Neuropharmacology. 2001;40(1):28-35. doi: 10.1016/s0028-3908(00)00112-x.
The role of AMPA and GluR5-containing kainate receptors in the development and expression of amygdala kindling was examined using the selective 2,3-benzodiazepine AMPA receptor antagonist GYKI 52466 [(1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2, 3-benzodiazepine] and the decahydroisoquinoline mixed AMPA receptor and GluR5 kainate receptor antagonist LY293558 {(3S,4aR,6R, 8aR)-6-[2-(1(2)H-tetrazole-5-yl)ethyl]decahydroisoquinoline- 3-carboxy lic acid)}. Administration of GYKI 52466 (5-40 mg/kg, intraperitoneally) and LY293558 (10-40 mg/kg, intraperitoneally) prior to daily kindling stimulation in mice produced a dose-dependent suppression of the rate of development of behavioral kindled seizure activity and reduced the duration of the stimulation-induced electrographic afterdischarge. In drug-free stimulation sessions after the initial drug-treatment sessions, there was an acceleration in the rate of kindling development compared with the rate during the preceding drug-administration period; the "rebound" rate was also greater than the kindling rate in saline-treated control animals. In fully kindled animals, both GYKI 52466 and LY293558 produced a dose-dependent suppression of evoked seizures (ED(50), 19.3 and 16.7 mg/kg, respectively). Although AMPA receptors appear to be critical to the expression of kindled seizures, since kindling development progressed despite the suppression of behavioral seizure activity, AMPA receptors are less important to the kindling process. LY293558 was modestly less effective at suppressing behavioral seizures during kindling and was not superior to GYKI 52466 in retarding the overall extent of kindling development, indicating that GluR5 kainate receptors do not contribute to epileptogenesis in this model.
使用选择性2,3 - 苯并二氮杂卓AMPA受体拮抗剂GYKI 52466 [（1 - （4 - 氨基苯基） - 4 - 甲基 - 7,8 - 亚甲基二氧基 - 5H - 2,3 - 苯并二氮杂卓]和十氢异喹啉混合AMPA受体及GluR5红藻氨酸受体拮抗剂LY293558 {（3S,4aR,6R,8aR） - 6 - [2 - （1（2）H - 四唑 - 5 - 基）乙基]十氢异喹啉 - 3 - 羧酸}，研究了含AMPA和GluR5的红藻氨酸受体在杏仁核点燃的发生和表达中的作用。在小鼠每日点燃刺激前腹腔注射GYKI 52466（5 - 40mg/kg）和LY293558（10 - 40mg/kg），可产生剂量依赖性地抑制行为性点燃癫痫活动的发展速度，并缩短刺激诱导的脑电图后放电的持续时间。在初始药物治疗阶段后的无药物刺激阶段，与之前给药期间的速度相比，点燃发展速度加快；“反弹”速度也高于生理盐水处理的对照动物的点燃速度。在完全点燃的动物中，GYKI 52466和LY293558均产生剂量依赖性地抑制诱发性癫痫发作（ED50分别为19.3和16.7mg/kg）。虽然AMPA受体似乎对点燃癫痫发作的表达至关重要，但由于尽管行为性癫痫活动受到抑制，点燃仍在发展，所以AMPA受体对点燃过程不太重要。LY293558在抑制点燃期间的行为性癫痫发作方面效果稍差，在延缓点燃发展的总体程度上并不优于GYKI 52466，这表明GluR5红藻氨酸受体在该模型中对癫痫发生没有作用。
