Allosteric Modulation of Sigma-1 Receptors Elicits Rapid Antidepressant Activity
文献类型：期刊论文
| 作者 | Wang, Yun1,2; Guo, Lin1; Jiang, Hua-Feng1; Zheng, Long-Tai1; Zhang, Ao3 ; Zhen, Xue-Chu1
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| 刊名 | CNS NEUROSCIENCE & THERAPEUTICS
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| 出版日期 | 2016-05 |
| 卷号 | 22期号:5页码:368-377 |
| 关键词 | Allosteric modulation Antidepressant Brain-derived neurotrophic factor Glycogen synthase kinase 3 Sigma-1 receptors |
| ISSN号 | 1755-5930 |
| DOI | 10.1111/cns.12502 |
| 文献子类 | Article |
| 英文摘要 | AimsSigma-1 receptors are involved in the pathophysiological process of several neuropsychiatric diseases such as epilepsy, depression. Allosteric modulation represents an important mechanism for receptor functional regulation. In this study, we examined antidepressant activity of the latest identified novel and selective allosteric modulator of sigma-1 receptor 3-methyl-phenyl-2, 3, 4, 5-tetrahydro-1H-benzo[d]azepin-7-ol (SOMCL-668). Methods and ResultsA single administration of SOMCL-668 decreased the immobility time in the forced swimming test (FST) and tailing suspended test in mice, which were abolished by pretreatment of sigma-1 receptor antagonist BD1047. In the chronic unpredicted mild stress (CUMS) model, chronic application of SOMCL-668 rapidly ameliorated anhedonia-like behavior (within a week), accompanying with the enhanced expression of brain-derived neurotrophic factor (BDNF) and phosphorylation of glycogen synthase kinase 3 (GSK3) (Ser-9) in the hippocampus. SOMCL-668 also rapidly promoted the phosphorylation of GSK3 (Ser-9) in an allosteric manner invitro. In the cultured primary neurons, SOMCL-668 enhanced the sigma-1 receptor agonist-induced neurite outgrowth and the secretion of BDNF. ConclusionSOMCL-668, a novel allosteric modulator of sigma-1 receptors, elicits a potent and rapid acting antidepressant effect. The present data provide the first evidence that allosteric modulation of sigma-1 receptors may represent a new approach for antidepressant drug discovery. |
| WOS关键词 | GLYCOGEN-SYNTHASE KINASE-3 ; MAJOR DEPRESSIVE DISORDER ; NEUROTROPHIC FACTOR ; RAT HIPPOCAMPUS ; KNOCKOUT MICE ; SKF83959 ; BDNF ; MECHANISM ; DISEASE ; INHIBITION |
| 资助项目 | National Science Foundation of China[81402905] ; National Science Foundation of China[81130023] ; National Science Foundation of China[81373382] ; National Science Foundation of China[81372688] ; National Basic Research Plan (973) of the Ministry of Science and Technology of China[2011CB504403] ; Priority Academic Program Development of Jiangsu Higher Education Institutes (PAPD)[00000000] ; Jiangsu key laboratory grant[BM2013003] |
| WOS研究方向 | Neurosciences & Neurology ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000374377600005 |
| 出版者 | WILEY-BLACKWELL |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276061]  |
| 专题 | 药理学第二研究室 药物化学研究室 |
| 通讯作者 | Zhen, Xue-Chu |
| 作者单位 | 1.Soochow Univ, Coll Pharmaceut Sci, Collaborat Innovat Ctr Brain Sci, Jiangsu Key Lab Translat Res Neuropsychiat Dis, 199 Renai Rd, Suzhou, Jiangsu, Peoples R China; 2.Xuzhou Med Coll, Dept Pharmacol, Jiangsu Key Lab New Drug Res & Clin Pharm, Xuzhou, Jiangsu, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Med Chem, Shanghai 200031, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Yun,Guo, Lin,Jiang, Hua-Feng,et al. Allosteric Modulation of Sigma-1 Receptors Elicits Rapid Antidepressant Activity[J]. CNS NEUROSCIENCE & THERAPEUTICS,2016,22(5):368-377. |
| APA | Wang, Yun,Guo, Lin,Jiang, Hua-Feng,Zheng, Long-Tai,Zhang, Ao,&Zhen, Xue-Chu.(2016).Allosteric Modulation of Sigma-1 Receptors Elicits Rapid Antidepressant Activity.CNS NEUROSCIENCE & THERAPEUTICS,22(5),368-377. |
| MLA | Wang, Yun,et al."Allosteric Modulation of Sigma-1 Receptors Elicits Rapid Antidepressant Activity".CNS NEUROSCIENCE & THERAPEUTICS 22.5(2016):368-377. |
入库方式： OAI收割
来源：上海药物研究所
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