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标题：Anticonvulsant Effect of (RS)-1-Aminoindan-1,5-dicarboxylic Acid on Pentetrazol-Induced Kindled Seizures in Mice
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作者：Yusuke Watanabe ; Yuko Kaida ; Kenshi Takechi 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2010
卷号：33
期号：4
页码：647-652
DOI：10.1248/bpb.33.647
出版社：The Pharmaceutical Society of Japan
摘要：The present study was undertaken to clarify the effect of group I metabotropic glutamate receptor (mGluR) antagonist, ( RS )-1-aminoindan-1,5-dicarboxylic acid (AIDA) on pentetrazol-induced kindled seizures. The mechanism of the anticonvulsant effect of AIDA was also studied. Mice were anesthetized with pentobarbital; the electrodes and guide cannula were chronically implanted into the cortex and lateral ventricle. In order to induce kindling, pentetrazol at a dose of 40 mg/kg was injected intraperitoneally once every 48 h. Behavioral and electroencephalographic (EEG) seizures were observed for 20 min following pentetrazol administration. Intracerebroventricular (i.c.v.) injection of AIDA (1000 nmol/site) resulted in a significant inhibitory effect on pentetrazol-induced kindled seizures, and this effect was antagonized by a group I mGluR agonist, ( RS )-3,5-dihydroxyphenylglycine (( RS )-3,5-DHPG). The effect of AIDA (200 nmol/site) on pentetrazol-induced kindled seizures was augmented by the simultaneous use of γ-aminobutyric acid (GABA) mimetic drugs, such as NNC-711 and diazepam. Moreover, the effect of AIDA (1000 nmol/site) on pentetrazol-induced kindled seizures was antagonized by a GABA_A receptor antagonist, bicuculline and a GABA_C receptor antagonist, (1,2,5,6-tetrahydropyridin-4-yl) methylphosphinic acid (TPMPA). It can be concluded that AIDA had an anticonvulsant effect on pentetrazol-induced kindled seizures, which was partially mediated by the GABAergic mechanism through GABA_A and GABA_C receptors.
关键词：metabotropic glutamate receptor;pentetrazol;kindling;(RS)-1-aminoindan-1,5-dicarboxylic acid;γ-aminobutyric acid