Compounds for inhibiting kainate-induced neuron damage

本项目新发现了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]和顺式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]等新型强效代谢型谷氨酸受体激动剂。它们比已知的mGluR激动剂(1S,3R)-ACPD更有效和选择性。当它们以相对低的剂量在大鼠的脑室内注射时，它们有中枢抑制作用。l - ccg - 1有效抑制点燃性癫痫发作，DCG-IV脑室内给药可有效延长氟烷麻醉大鼠的恢复时间。大鼠经长时间脑室内灌注DCG-IV（24-240 pmol /大鼠，17小时）后，向大鼠脑室内灌注2 nmol的kainic酸（KA）。大鼠脑室预灌注DCG-IV可显著抑制ka诱导的边缘运动癫痫和海马CA3区、杏仁核、隔区神经元损伤。特别是，相当低剂量的DCG-IV是有效的，尽管相对高剂量的DCG-IV本身诱导了大鼠扣带皮层的选择性神经元损伤。一针DCG-IV并没有抑制那么多的边缘运动癫痫和神经元损伤。

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.