Amphetamine Derivatives as Potent Central Nervous System Multitarget SERT/NET/H<sub>3</sub> Agents: Synthesis and Biological Evaluation
In this research, a variety of novel amphetamine derivatives were synthesized and assessed for their potential as multifaceted antidepressant agents. Among these compounds, compound <b>11b</b> demonstrated potent inhibitory effects on both serotonin and noradrenaline transporters (SERT/N...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-11-01
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| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/29/22/5240 |
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| Summary: | In this research, a variety of novel amphetamine derivatives were synthesized and assessed for their potential as multifaceted antidepressant agents. Among these compounds, compound <b>11b</b> demonstrated potent inhibitory effects on both serotonin and noradrenaline transporters (SERT/NET) and high affinity for histamine H<sub>3</sub> receptor (H<sub>3</sub>R), and displayed low affinity for off-target receptors (H1, α1) and hERG channels, which can reduce the prolongation of the QT interval. Molecular docking studies offered a rational binding model of compound <b>11b</b> when it forms a complex with SERT, NET, and the histamine H<sub>3</sub> receptor. In vivo behavioral studies, compound <b>11b</b> dose-dependently reduced the immobility duration in the mouse FST and TST assays without a stimulatory effect on the locomotor activity. Furthermore, compound <b>11b</b> had a favorable pharmacokinetic profile in rats. Thus, compound <b>11b</b> has the potential to develop a novel class of drugs for the treatment of depression. |
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| ISSN: | 1420-3049 |