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The antidepressant-like effect and proposed mechanism of action of TPN672MA, a novel serotonin-dopamine receptor modulator for the treatment of schizophrenia

文献类型：期刊论文

作者Cheng, Jiaxin2,3; Wu, Chunhui1; Wang, Yu2,3; Wang, Zhen2,3; He, Yang2,3; Shen, Jingshan2,3
刊名PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
出版日期2024-09-01
卷号242页码:13
关键词TPN672MA 5-HT 1A receptor agonist D 2 /D 3 receptor partial agonist 5-HT 2A receptor antagonist Antidepressant-like Mechanism
ISSN号0091-3057
DOI10.1016/j.pbb.2024.173809
通讯作者He, Yang(chengjiaxin@simm.ac.cn) ; Shen, Jingshan(shenjingshan@simm.ac.cn)
英文摘要TPN672MA, an innovative antipsychotic drug candidate currently in clinical trials, acts as a dopamine D2/D3 receptor partial agonist, serotonin 5-HT1A receptor agonist, and serotonin 5-HT2A receptor antagonist. Preclinical investigations have demonstrated its potential in treating the core symptoms of schizophrenia. The present study highlights TPN672MA's significant antidepressant-like effects in classical behavioral models, such as the chronic social defeat stress paradigm. The pronounced 5-HT1A receptor agonism and D2/D3 receptor partial agonism of TPN672MA likely contribute to its therapeutic effects in depression. Additionally, TPN672MA's antidepressantlike efficacy may be linked to its ability to enhance the expression levels of brain-derived neurotrophic factor (BDNF) and postsynaptic density protein-95 (PSD95) in the hippocampus. Furthermore, TPN672MA displayed a more rapid onset of antidepressant-like action. In conclusion, TPN672MA represents a promising new drug candidate for the treatment of symptoms of schizophrenia and depression.
WOS关键词MESSENGER-RNA EXPRESSION ; NEGATIVE SYMPTOMS ; TRANSPORTER BINDING ; DEPRESSION ; BEHAVIOR ; STRESS ; MICE ; RAT ; HYPOTHERMIA ; ANTAGONIST
资助项目Lingang Laboratory, China[LG-GG-202204-01] ; National Science and Technology Innovation 2030 Major Program of China[2021ZD0200900]
WOS研究方向Behavioral Sciences ; Neurosciences & Neurology ; Pharmacology & Pharmacy
语种英语
WOS记录号WOS:001266076200001
出版者PERGAMON-ELSEVIER SCIENCE LTD
源URL[http://119.78.100.183/handle/2S10ELR8/312279]  
专题新药研究国家重点实验室
通讯作者He, Yang; Shen, Jingshan
作者单位1.Vigonvita Shanghai Life Sci Co Ltd, Shanghai 200000, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Cheng, Jiaxin,Wu, Chunhui,Wang, Yu,et al. The antidepressant-like effect and proposed mechanism of action of TPN672MA, a novel serotonin-dopamine receptor modulator for the treatment of schizophrenia[J]. PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR,2024,242:13.
APA Cheng, Jiaxin,Wu, Chunhui,Wang, Yu,Wang, Zhen,He, Yang,&Shen, Jingshan.(2024).The antidepressant-like effect and proposed mechanism of action of TPN672MA, a novel serotonin-dopamine receptor modulator for the treatment of schizophrenia.PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR,242,13.
MLA Cheng, Jiaxin,et al."The antidepressant-like effect and proposed mechanism of action of TPN672MA, a novel serotonin-dopamine receptor modulator for the treatment of schizophrenia".PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR 242(2024):13.

入库方式： OAI收割

来源：上海药物研究所

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