Structural Pharmacology of Bufotenine Derivatives in Activating the 5-HT1A Receptor for Therapeutic Potential in Depression and Anxiety
文献类型：期刊论文
| 作者 | Li, Shu-jie1,3,4,5; Yuan, Qing-ning1,3,4; Wu, Wen-yuan3,4; Chen, Zhi-han3,4; Chen, Duo3,4; Shan, Hong1; Chu, Qin-yu2; Hu, Wen1; Wu, Kai1; Liu, Tao1 |
| 刊名 | RESEARCH
 |
| 出版日期 | 2025-12-23 |
| 卷号 | 8页码:16 |
| ISSN号 | 2096-5168 |
| DOI | 10.34133/research.0987 |
| 英文摘要 | The 5-HT1A receptor is a critical target in the treatment of depression and anxiety. Bufotenine derivatives, such as 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), 5-hydroxy-N,N-dimethyltryptamine (5-OH-DMT), and 5-hydroxy-N,N,N-dimethyltryptamine-derived from traditional Chinese medicine-have shown antidepressant potential. However, the structural basis of their interaction with 5-HT1A and their pharmacological profiles remain incompletely understood. This study investigated bufotenine derivatives acting on multiple serotonin receptors, highlighting 5-HT1A as a key mediator of antidepressant effects while recognizing 5-HT2A as primarily responsible for hallucinogenic outcomes, to identify candidates with therapeutic efficacy but reduced hallucinogenic liability. We determined the cryo-electron microscopy structures of 5-HT1A bound to selected bufotenine derivatives. Functional assays in mice, including behavioral tests and receptor activation studies, were used to evaluate the antidepressant of each compound. Structural analysis revealed that all bufotenine derivatives engage conserved motifs within the 5-HT1A binding pocket, with 5-OH-DMT displaying a distinct interaction pattern. Behavioral assays showed that 5-OH-DMT and 5-MeO-DMT retained strong antidepressant and anxiolytic effects. These pharmacological differences correlate with their unique receptor binding conformation. This study delineated the structural pharmacology of bufotenine derivatives at the 5-HT1A receptor, identifying 5-OH-DMT and 5-MeO-DMT as promising antidepressant and anxiolytic candidates. The findings establish a molecular framework for the development of next-generation nonhallucinogenic therapeutics aimed at 5-HT1A. |
| WOS关键词 | MICE LACKING ; SEROTONIN ; TRYPTAMINES ; MODEL ; PSYCHEDELICS ; PSILOCYBIN ; 5-MEO-DMT ; SOFTWARE ; BINDING |
| 资助项目 | National Natural Science Foundation of China[82404881] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:001644654100001 |
| 出版者 | AMER ASSOC ADVANCEMENT SCIENCE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/322435]  |
| 专题 | 国家级研究中心_原创新药研究全国重点实验室 |
| 通讯作者 | Zhou, Jing; Duan, Jia; Duan, Jin-ao; Xu, H. Eric; Ma, Hong-yue |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.UCAS, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China 3.Nanjing Univ Chinese Med, Coll Pharm, Jiangsu Collaborat Innovat Ctr Chinese Med Resourc, Nanjing 210023, Peoples R China 4.Nanjing Univ Chinese Med, Coll Pharm, Jiangsu Key Lab High Technol Res TCM Formulae, Nanjing 210023, Peoples R China 5.Fujian Med Univ, Union Hosp, Dept Tradit Chinese Med, Fuzhou 350000, Fujian, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Shu-jie,Yuan, Qing-ning,Wu, Wen-yuan,et al. Structural Pharmacology of Bufotenine Derivatives in Activating the 5-HT1A Receptor for Therapeutic Potential in Depression and Anxiety[J]. RESEARCH,2025,8:16. |
| APA | Li, Shu-jie.,Yuan, Qing-ning.,Wu, Wen-yuan.,Chen, Zhi-han.,Chen, Duo.,...&Ma, Hong-yue.(2025).Structural Pharmacology of Bufotenine Derivatives in Activating the 5-HT1A Receptor for Therapeutic Potential in Depression and Anxiety.RESEARCH,8,16. |
| MLA | Li, Shu-jie,et al."Structural Pharmacology of Bufotenine Derivatives in Activating the 5-HT1A Receptor for Therapeutic Potential in Depression and Anxiety".RESEARCH 8(2025):16. |
入库方式： OAI收割
来源：上海药物研究所
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