Science—中国科学家发现新型快速起效的抗抑郁药物：靶向于DRN的SERT-nNOS复合物

中文摘要

抑郁症（MDD）是最常见的精神障碍之一。研究人员设计了一种快速起效的抗抑郁药，它通过破坏中缝背核（DRN）中5-羟色胺转运体（SERT）和神经元一氧化氮合酶（nNOS）之间的相互作用而起作用。慢性不可预测的轻度应激（CMS）选择性地增加了小鼠DRN中的SERT-nNOS复合物。DRN中SERT-nNOS相互作用的增强导致抑郁样表型，并解释了CMS诱导的抑郁行为。破坏SERT-nNOS相互作用通过增强前脑回路中的5-羟色胺信号从而产生快速的抗抑郁作用。研究人员发现了一种小分子化合物ZZL-7，它在给药后2小时即产生抗抑郁作用，没有不良副作用。该化合物或类似试剂可作为MDD的新的快速治疗药物。

英文摘要

Major depressive disorder (MDD) is one of the most common mental disorders. We designed a fast-onset antidepressant that works by disrupting the interaction between the serotonin transporter (SERT) and neuronal nitric oxide synthase (nNOS) in the dorsal raphe nucleus (DRN). Chronic unpredictable mild stress (CMS) selectively increased the SERT-nNOS complex in the DRN in mice. Augmentation of SERT-nNOS interactions in the DRN caused a depression-like phenotype and accounted for the CMS-induced depressive behaviors. Disrupting the SERT-nNOS interaction produced a fast-onset antidepressant effect by enhancing serotonin signaling in forebrain circuits. We discovered a small-molecule compound, ZZL-7, that elicited an antidepressant effect 2 hours after treatment without undesirable side effects. This compound, or analogous reagents, may serve as a new, rapidly acting treatment for MDD.

参考文献：Design of fast-onset antidepressant by dissociating SERT from nNOS in the DRN. Science. 2022 Oct 28;378(6618):390-398. doi: 10.1126/science.abo3566. Epub 2022 Oct 27.

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