Antipsychotic action of selective group II metabotropic glutamate receptor agonist MGS0008 and MGS0028 on conditioned avoidance responses in the rat.

Takamori K; Hirota S; Chaki S; Tanaka M

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Antipsychotic action of selective group II metabotropic glutamate receptor agonist MGS0008 and MGS0028 on conditioned avoidance responses in the rat.

机译：选择性组II代谢型谷氨酸受体激动剂MGS0008和MGS0028对大鼠条件性回避反应的抗精神病作用。

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The present study was designed to investigate the antipsychotic-like effects of selective group II metabotropic glutamate receptor (mGluR) agonists, 5-[2-[4-(6-fluoro-1H-indole-3-yl) piperidin-1-yl]ethyl]-4-(4-fluorophenyl)thiazole-2-carboxylic acid amide (MGS0008) and (1R, 2S, 5S, 6S)-2-amino-6-fluoro-4-oxobicyclo[3.1.0]hexane-2,6-dicarboxylic acid monohydrate (MGS0028) on conditioned avoidance responses in rats. MGS0008 (1, 3 and 10 mg/kg, p.o.) and MGS0028 (0.3, 1 and 3 mg/kg, p.o.) significantly and reduced conditioned avoidance responses in a dose-dependent fashion. Similar effects were seen with LY418426 (0.3, 1 and 3 mg/kg, p.o.), but not with LY354740 (3, 10 and 30 mg/kg, p.o.), both of which are selective agonists for group II mGluR. Since this effect is seen with a wide range of antipsychotics, such as haloperidol and clozapine [Life Sciences 71 (2002) 947], group II mGluR agonists deserve further attention for possible antipsychotic activity.

机译：本研究旨在研究选择性II型代谢型谷氨酸受体（mGluR）激动剂5- [2- [4-（6-氟-1H-吲哚-3-基）哌啶-1-基]的抗精神病样作用。 ]乙基] -4-（4-氟苯基）噻唑-2-羧酸酰胺（MGS0008）和（1R，2S，5S，6S）-2-氨基-6-氟-4-氧代双环[3.1.0]己烷- 2,6-二羧酸一水合物（MGS0028）对大鼠的条件回避反应。 MGS0008（1、3和10 mg / kg，p.o.）和MGS0028（0.3，1和3 mg / kg，p.o.）以剂量依赖的方式显着降低了条件回避反应。 LY418426（0.3、1和3 mg / kg，p.o.）观察到类似的效果，LY354740（3，10和30 mg / kg，p.o.）观察不到，两者都是II组mGluR的选择性激动剂。由于这种作用可在多种抗精神病药（如氟哌啶醇和氯氮平）中观察到[Life Sciences 71（2002）947]，因此II组mGluR激动剂可能具有抗精神病活性。

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《Life sciences》 |2003年第13期|共8页
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Takamori K; Hirota S; Chaki S; Tanaka M;
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正文语种 eng
中图分类基础医学;
关键词
Antipsychotic Agents; Avoidance Learning; Behavior; Animal; Bicyclo Compounds; 抗精神病剂; 回避学习; 行为; 动物; 二环化合物; 二羧酸类; 兴奋性氨基酸激动剂;

机译：Antipsychotic Agents;Avoidance Learning;Behavior;Animal;Bicyclo Compounds;抗精神病剂;回避学习;行为;动物;二环化合物;二羧酸类;兴奋性氨基酸激动剂;

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1. Antipsychotic action of selective group II metabotropic glutamate receptor agonist MGS0008 and MGS0028 on conditioned avoidance responses in the rat. [J] . Takamori K, Hirota S, Chaki S, Life sciences . 2003,第13期

机译：选择性组II代谢型谷氨酸受体激动剂MGS0008和MGS0028对大鼠条件性回避反应的抗精神病作用。
2. Group II selective metabotropic glutamate receptor agonists and local cerebral glucose use in the rat. [J] . Lam AG, Monn JA, Schoepp DD, Journal of Cerebral Blood Flow and Metabolism: Official Journal of the International Society of Cerebral Blood Flow and Metabolism . 1999,第10期

机译：第二组选择性代谢型谷氨酸受体激动剂和大鼠局部脑葡萄糖的使用。
3. Selective action of (-)-2-oxa-4-aminobicyclo(3.1.0)hexane-4,6-dicarboxylate (LY379268), a group II metabotropic glutamate receptor agonist, on basal and phencyclidine-induced dopamine release in the nucleus accumbens shell. [J] . Greenslade RG, Mitchell SN Neuropharmacology . 2004,第1期

机译：II型代谢型谷氨酸受体激动剂（-）-2-oxa-4-氨基双环（3.1.0）己烷-4,6-二羧酸己烷（LY379268）对伏隔核中基础和苯环利定诱导的多巴胺释放的选择性作用贝壳。
4. Inverse agonists to explore the mechanisms of metabotropic glutamate receptor activity [C] . L. Prezeau, M.L. Parmentier, R Carroll, Fundaci髇 Dr. Antonio Esteve . 2003

机译：反向激动剂探讨代谢谷氨酸受体活性的机制
5. Role of the Group I metabotropic glutamate receptors in prepulse inhibition of the startle response. [D] . Brody, Suzanne Amy. 2003

机译：I组代谢型谷氨酸受体在惊吓反应的脉冲前抑制中的作用。
6. Preclinical disposition of MGS0274 besylate a prodrug of a potent group II metabotropic glutamate receptor agonist MGS0008 for the treatment of schizophrenia [O] . Kohnosuke Kinoshita, Motoki Ochi, Katsuya Iwata, 2019

机译：MGS0274苯磺酸盐的临床前处置它是强效的II型代谢型谷氨酸受体激动剂MGS0008的前药用于治疗精神分裂症
7. Metabotropic glutamate receptor 3 neuroprotection A. Berent-Spillson and J. W. Russell Received June 12, 2006; revised manuscript received October 3, 2006; accepted October 5, 2006. Address correspondence and reprint requests to James W. Russell, Department of Neurology, University of Maryland School of Medicine, 22 South Greene Street, Baltimore, MD 21201-1595, USA. E-mail: jruss@umich.edu Abbreviations used : APDC , 2 R ,4 R -4-aminopyrrolidine-2,4-dicarboxylate (specific metabotropic glutamate receptor 3 agonist) ; BSO , buthionine sulfoximine (GSH synthesis inhibitor) ; caspase , cysteine-requiring aspartate protease ; CysGly , cysteinylglycine (GSH degradation product) ; DAPI , 4′-6-diamidino-2-phenylindole ; DCF , dichlorodihydrofluorescein ; DCFDA , 5-(and 6)-chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate, acetyl ester ; DHE , dihydroethidium ; DRG , dorsal root ganglion ; FCCP , carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (electron transport uncoupler) ; GCP II/III , glutamate carboxypeptidase II/III ; GSH , glutathione ; GSH-EE , glutathione ethyl ester ; GST , glutathione-s-transferase ; H 2 O 2 , hydrogen peroxide ; HBSS , Hank’s balanced salt solution ; JC-1 , 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolylcarbocyanine iodide ; MCB , monochlorobimane ; mGluR , metabotropic glutamate receptor ; NAAG , N -acetyl-aspartyl-glutamate ; PBS , phosphate-buffered saline ; PCD , programmed cell death ; Rh123 , rhodamine123 ; ROS , reactive oxygen species ; δψ μ , inner mitochondrial membrane potential . Metabotropic glutamate receptor 3 protects neurons from glucose-induced oxidative injury by increasing intracellular glutathione concentration [O] . Berent-Spillson Alison, Russell James W. 2007

机译：代谢型谷氨酸受体3神经保护a. Berent-spillson和J. W. Russell于2006年6月12日收到;修订稿于2006年10月3日收到; 2006年10月5日接受。美国马里兰州巴尔的摩市南格林街22号，马里兰大学医学院神经病学系James W. Russell的地址通信和重印申请。电子邮件：jruss@umich.edu使用的缩写：apDC，2R，4R-4-氨基吡咯烷-2,4-二羧酸酯（特异性代谢型谷氨酸受体3激动剂）; BsO，丁硫氨酸亚砜亚胺（GsH合成抑制剂）;半胱天冬酶，半胱氨酸需要的天冬氨酸蛋白酶; CysGly，半胱氨酰甘氨酸（GsH降解产物）; DapI，4'-6-二脒基-2-苯基吲哚; DCF，二氯二氢荧光素; DCFDa，5-（和6） - 氯甲基-2'，7'-二氯二氢荧光素二乙酸酯，乙酰酯; DHE，二氢乙锭; DRG，背根神经节; FCCp，羰基氰化物4-（三氟甲氧基）苯腙（电子传输解偶联剂）; GCp II / III，谷氨酸羧肽酶II / III;谷胱甘肽;谷胱甘肽; GsH-EE，谷胱甘肽乙酯; GsT，谷胱甘肽-s-转移酶; H 2 O 2，过氧化氢; HBss，Hank的平衡盐溶液; JC-1,5,5'，6,6'-四氯-1,1'，3,3'-四乙基苯并咪唑基酞菁碘化物; mCB，monochlorobimane; mGluR，代谢型谷氨酸受体; NaaG，N-乙酰基 - 天冬氨酰谷氨酸; pBs，磷酸盐缓冲盐水; pCD，程序性细胞死亡; Rh123，罗丹明123;活性氧，活性氧; δψμ，线粒体内膜电位。代谢型谷氨酸受体3通过增加细胞内谷胱甘肽浓度来保护神经元免受葡萄糖诱导的氧化损伤
8. Group II Metabotropic Glutamate Receptors as Potential Pharmaceutical Targets for Neurofibroma Formation [R] . Stern, M. 2011

机译：第II组代谢型谷氨酸受体作为神经纤维瘤形成的潜在药物靶标

Antipsychotic action of selective group II metabotropic glutamate receptor agonist MGS0008 and MGS0028 on conditioned avoidance responses in the rat.

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