Anticonvulsant actions of LY 367385 ((+)-2-methyl-4-carboxyphenylglycine) and AIDA ((RS)-1-aminoindan-1,5-dicarboxylic acid)
Anticonvulsant actions of LY 367385 ((+)-2-methyl-4-carboxyphenylglycine) and AIDA ((RS)-1-aminoindan-1,5-dicarboxylic acid)
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DOI：
10.1016/s0014-2999(99)00014-x
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发表时间：
1999-02-26
影响因子：
5
通讯作者：
Meldrum, BS
中科院分区：
文献类型：
--
作者：
Chapman, AG;Yip, PK;Meldrum, BS
我们研究了两种对 mGlu(1) 受体具有选择性的 I 类代谢型谷氨酸受体拮抗剂在三种全身性惊厥或失神性癫痫啮齿动物模型中的作用。 LY 367385 ((+)-2-甲基-4-羧基苯基甘氨酸) 和 AIDA ((RS)-1-氨基茚满-1,5-二羧酸) 已被脑室内 (i.c.v.) 给予 DBA/2 小鼠和昏睡小鼠 (lh/lh)，并局部注射到遗传性癫痫倾向大鼠 (GEPR) 的下丘。在 DBA/2 小鼠中，两种化合物对声音诱发的阵挛性癫痫发作产生快速、短暂的抑制（LY 367385：ED50 = 12 nmol，静脉注射，5 分钟；AIDA：ED50 = 79 nmol，静脉注射，15 分钟）。在昏睡小鼠中，在给予 AIDA（500 nmol，i.c.v.）后 < 30 至 > 150 分钟以及给予 LY 367385（250 nmol，i.c.v.）后 30 至 > 150 分钟内，两种化合物均显着降低脑电图上自发尖峰和波放电的发生率。 LY 367385，50 nmol，抑制自发尖峰放电和波放电 30 至 60 分钟。在遗传性癫痫易感大鼠中，这两种化合物都能减少声音诱发的阵挛性癫痫发作。 LY 367385，双侧 160 nmol，在 2-4 小时后完全抑制阵挛性癫痫发作。 AIDA 双侧 100 nmol 后 30 分钟完全有效。结论是，mGlu(1) 受体拮抗剂是潜在的抗惊厥药物，mGlu(1) 受体的激活可能导致多种癫痫综合征。 (C) 1999 Elsevier Science B.V. 保留所有权利。
We have studied the effects in three rodent models of generalised convulsive or absence epilepsy of two antagonists of group I metabotropic glutamate receptors that are selective for the mGlu(1) receptor. LY 367385 ((+)-2-methyl-4-carboxyphenylglycine) and AIDA ((RS)-1-aminoindan-1,5-dicarboxylic acid) have been administered intracerebroventricularly (i.c.v.) to DBA/2 mice and lethargic mice (lh/lh), and focally into the inferior colliculus of genetically epilepsy prone rats (GEPR). In DBA/2 mice both compounds produce a rapid, transient suppression of sound-induced clonic seizures (LY 367385: ED50 = 12 nmol, i.c.v., 5 min; AIDA: ED50 = 79 nmol, i.c.v., 15 min). In lethargic mice both compounds significantly reduce the incidence of spontaneous spike and wave discharges on the electroencephalogram, from < 30 to > 150 min after the administration of AIDA, 500 nmol, i.c.v., and from 30 to > 150 min after the administration of LY 367385, 250 nmol, i.c.v. LY 367385, 50 nmol, suppresses spontaneous spike and wave discharges from 30 to 60 min. In genetically epilepsy prone rats both compounds reduce sound-induced clonic seizures. LY 367385, 160 nmol bilaterally, fully suppresses clonic seizures after 2-4 h. AIDA is fully effective 30 min after 100 nmol bilaterally. It is concluded that antagonists of mGlu(1) receptors are potential anticonvulsant agents and that activation of mGlu(1) receptors probably contributes to a variety of epileptic syndromes. (C) 1999 Elsevier Science B.V. All rights reserved.