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Compounds for inhibiting kainate-induced neuron damage

用于抑制红藻氨酸诱导的神经元损伤的化合物

基本信息

批准号：
04836029
负责人：
ISHIDA Michiko
金额：
$ 1.22万
依托单位：
The Tokyo Metropolitan Institute of Medical Science
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1993
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04836029/
关键词：
metabotropic glutamate receptor neuron damage kainic acid DCG-IV L-CCG-I Excitatory amino acid limbic motor seizures (8)hippocampus CA3 脳虚血

项目摘要

Some novel and potent metabotropic glutamate receptor (mGluR) agonists, such as L-CCG-I [2S,1'S,2'S)-2-(carboxycyclopropyl)glycine], and its analogues, DCG-IV[(2S,1'R,2'R,3'R)-2-(2,3-dicarboxycylopropyl)glycine] and cis-MCG-I[(2S,1'S,2'R,3'R)-2-(2-carboxy-3-methoxymethylcyclopropyl)glycine], were newly found in the present project. They were more potent and selective than a known mGluR agonist, (1S,3R)-ACPD.They have central depressant actions in the rat when they were intraventricularly administered at relarively low doses. L-CCG-I effectively inhibited kindling seizures, and intraventricular administration of DCG-IV effectively prolonged the recovery from halothane anesthesia in the rat. After prolonged intraventricular infusion of DCG-IV(24-240 pmoles/rat, 17hrs) to the rat, 2 nmoles of kainic acid(KA) was infused into the rat ventricle. The KA-induced limbic motor seizures and neuron damage in the hippocampus CA3 area, amygdala and septum were considerably inhibited by pre-infusion of DCG-IV into the rat ventricle. In particular, fairly low doses of DCG-IV were effective, although relatively high doses of DCG-IV per se induced selective neuron damage in the rat cingulate cortex. One shot of DCG-IV did not inhibit so much limbic motor seizures and neuron damage.

本文报道了新发现的代谢型谷氨酸受体（mGluR）激动剂L-CCG-I [（2S，1 ′ S，2 ′ S）-2-（羧基环丙基）甘氨酸]及其类似物DCG-IV[（2S，1 ′ R，2 ′ R，3 ′ R）-2-（2，3-二羧基环丙基）甘氨酸]和cis-MCG-I[（2S，1 ′ S，2 ′ R，3 ′ R）-2-（2-羧基-3-甲氧基甲基环丙基）甘氨酸]。它们比已知的mGluR激动剂（1 S，3R）-ACPD更有效，选择性更强，在大鼠脑室注射较低剂量时有中枢兴奋作用。L-CCG-I可有效抑制大鼠点燃发作，DCG-IV脑室给药可有效延长氟烷麻醉后的恢复时间。在向大鼠长时间脑室内输注DCG-IV（24-240皮摩尔/大鼠，17小时）后，将2纳摩尔红藻氨酸（KA）输注到大鼠心室中。脑室预注DCG-IV可明显抑制KA诱发的边缘运动性癫痫发作及海马CA 3区、杏仁核和隔区神经元的损伤。特别是，相当低剂量的DCG-IV是有效的，虽然相对高剂量的DCG-IV本身诱导大鼠扣带皮层中的选择性神经元损伤。一针DCG-IV并不能抑制如此多的边缘运动癫痫发作和神经元损伤。