2. Academic Validation
  3. Methylenedioxy open-loop and closed-loop aporphines designed for the evaluation of potential antidepressants

Methylenedioxy open-loop and closed-loop aporphines designed for the evaluation of potential antidepressants

  • Eur J Med Chem. 2025 Nov 5:297:117969. doi: 10.1016/j.ejmech.2025.117969.
Yili Wan 1,  Chunyu Wu 2,  Benqin Tang 3,  Li Chen 4,  Jianbo Sun 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Nanjing, 211198, China; Institute of Flow Chemistry and Engineering, School of Chemistry and Materials, Jiangxi Normal University, 99 Ziyang Road, Nanchang, 330022, China.
  • 2 State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Nanjing, 211198, China.
  • 3 Research Centre for Chinese Medicine Innovation, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, 999077, China. Electronic address: tangbenqincy@gmail.com.
  • 4 State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Nanjing, 211198, China. Electronic address: chenli627@cpu.edu.cn.
  • 5 State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Nanjing, 211198, China. Electronic address: sunjianbo@cpu.edu.cn.
PMID: 40663971 DOI: 10.1016/j.ejmech.2025.117969
Abstract

A series of methylenedioxy open-loop and closed-loop aporphine derivatives were designed and synthesized to systematically compare their antidepressant effects and addiction potential. The methylenedioxy open-loop derivatives showed slightly superior antidepressant activity compared with their closed-loop counterparts. Notably, the open-loop derivative Ie demonstrated significantly lower addictive potential than the closed-loop derivative IIe, suggesting that the open-loop methylenedioxy moiety may attenuate the addiction liability of related synthetic antidepressants. Further investigations revealed a significant increase in brain 5-hydroxytryptamine (5-HT) levels following treatment with Ie, which may be attributed to its synergistic effect on downregulating the expression of 5-HT2A receptors (5-HT2AR) and serotonin transporters (SERT). Collectively, the results indicate that Ie possesses the most potent and rapid antidepressant activity among the synthesized compounds, outperforming fluoxetine (Flu) in both efficacy and onset of action. These findings suggest that methylenedioxy open-loop aporphines-particularly Ie-hold strong promise as drug candidates for central nervous system modulation.

Keywords

5-HT level; 5-HT(2A)R; Antidepressant; Aporphine analogs; SERT.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z