Patients with depression with sleep problems have functional abnormalities of 5-HT and NE neurotransmitters, and the NaSSA class antidepressant mianserin has an ameliorative effect on sleep problems along with antidepressant. However, whether mianserin can improve cognitive function in patients still needs to be explored. The benzodiazepine lorazepam can play a central inhibitory role and has good therapeutic effect on insomnia. The mechanism of action of mianserin and lorazepam is different, and there are few comparative studies related to the combination of the two with SSRI drugs for the treatment of depressed patients with sleep problems, and it is unclear whether there are differences in their efficacy and safety. Therefore, to address the above scientific questions, this study was designed to include 100 patients aged 18-60 years with depression with sleep problems, randomly divided into two groups and treated with mianserin + escitalopram or lorazepam + escitalopram, respectively, and followed up for 8 weeks to assess depression and anxiety symptoms, sleep, cognitive function and drug safety. To compare the efficacy and safety of the two regimens in depressed patients with sleep problems and to provide a scientific basis for clinical intervention in depressed patients with sleep problems.

开始日期2024-07-01

申办/合作机构

上海市精神卫生中心（上海市心理咨询培训中心）

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100 项与 NET x α-adrenergic receptor 相关的临床结果

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100 项与 NET x α-adrenergic receptor 相关的转化医学

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0 项与 NET x α-adrenergic receptor 相关的专利（医药）

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213

项与 NET x α-adrenergic receptor 相关的文献（医药）

2025-05-01·Molecular Neurobiology

Selective Noradrenergic Activation of BDNF Translation by Mirtazapine

Article

作者: Santoni, Letizia ; Tongiorgi, Enrico ; Ciraci, Viviana

Antidepressants are known for their neurotrophic effects, particularly through the regulation of brain-derived neurotrophic factor (BDNF) expression. Mirtazapine, a tetracyclic noradrenergic and specific serotonergic antidepressant (NaSSA) has been observed to upregulate BDNF, though its underlying mechanism remains unclear. In this study, we used the human neuroblastoma SH-SY5Y cell line to investigate whether mirtazapine could enhance BDNF translation by modulating serotonin and/or norepinephrine and their receptors. A 1-h stimulation with 1 or 10 µM mirtazapine led to downregulation of serotonergic receptors 5HT1A, while increasing ADRA2A and ADRB2 receptors. Mirtazapine at 10 µM upregulated endogenous BDNF after 3h, but not 1h stimulation. To investigate the translation of major BDNF transcripts, we used chimeric BDNF-luciferase constructs with the untranslated 5'UTR exons I, IIc, IV, or VI, and the long version of the 3'UTR. Luciferase assays and Western blotting revealed that mirtazapine selectively enhanced exon-IIc-BDNF-long3'UTR-Luciferase translation. This increase was associated with norepinephrine release and was inhibited by blocking ADRA2A or ADRB2 adrenoceptors for the exon-IIc-BDNF-long3'UTR-Luciferase, and ADR2B for endogenous BDNF. These findings provide a new perspective on the critical role of the noradrenergic system in mediating mirtazapine's effects on BDNF translation. We propose a novel mechanism of action in which mirtazapine promotes norepinephrine release and noradrenergic responses by upregulating ADRA2A and ADRB2 while downregulating serotonergic receptors.

2025-04-01·Biological Psychiatry

Noradrenaline modulates central amygdala GABA transmission and alcohol drinking in female rats

Article

作者: Hughes, Kiley ; Zalfa, Cristina ; Gandhi, Pauravi ; Borgonetti, Vittoria ; Rodriguez, Larry ; Erikson, Chloe Michelle ; Bajo, Michal ; Martin-Fardon, Rémi ; Vozella, Valentina ; Roberto, Marisa ; Barchiesi, Riccardo ; Flores-Ramirez, Francisco J ; Vlkolinsky, Roman ; Cruz, Bryan ; Mayfield, R Dayne ; Anjos-Santos, Alexia

BACKGROUNDAlcohol use disorder (AUD) is a chronic relapsing disorder and a leading preventable cause of death worldwide. The central nucleus of the amygdala (CeA) is a hub for stress and AUD. Noradrenaline (norepinephrine; NE) regulates the brain's response to stress and alcohol. We previously reported that α1 adrenergic receptors drive moderate alcohol intake, while β receptors contribute to excessive drinking associated with dependence in male rats.METHODSHere, we determined that alcohol dependence and withdrawal alter the CeA noradrenergic system in female rats using ex vivo electrophysiology, in situ hybridization, site-specific behavioral pharmacology, and RNA-sequencing data from postmortem CeA samples obtained from female donors with and without AUD.RESULTSNE bidirectionally (increase and decrease) modulated CeA GABAergic transmission via both α1 and β receptors. Prazosin, an α1 receptor antagonist, reduced moderate alcohol intake in non-dependent female rats and excessive drinking in dependent females, while propranolol, a β receptor antagonist, only reduced excessive drinking in dependent females. While withdrawal produced a partial functional recovery of the NE modulation of the CeA, some of the cellular patterns of adrenergic receptor mRNA expression persist. Although we did not observe any differences in adrenergic receptor gene expression in the CeA from our human AUD donors, we found a downregulation of ADRA1A in the basolateral amygdala and the dorsolateral prefrontal cortex, compared to controls.CONCLUSIONSAmygdalar α1 and β adrenergic receptors are key neural substrates of AUD. Our results support ongoing development of receptor-specific medication for AUD and highlight promising efficacy in females.

2025-04-01·Cell Stem Cell

Interferon-responsive intestinal BEST4/CA7+ cells are targets of bacterial diarrheal toxins

Article

作者: Akkerman, Ninouk ; Spoelstra, Willem Kasper ; Dayton, Talya ; van Zon, Jeroen S ; Lin, Lin ; Tans, Sander J ; Clevers, Hans ; Krueger, Daniel ; Wang, Daisong ; van Es, Johan H

BEST4/CA7⁺ cells of the human intestine were recently identified by single-cell RNA sequencing. While their gene expression profile predicts a role in electrolyte balance, BEST4/CA7⁺ cell function has not been explored experimentally owing to the absence of BEST4/CA7⁺ cells in mice and the paucity of human in vitro models. Here, we establish a protocol that allows the emergence of BEST4/CA7⁺ cells in human intestinal organoids. Differentiation of BEST4/CA7⁺ cells requires activation of Notch signaling and the transcription factor SPIB. BEST4/CA7⁺ cell numbers strongly increase in response to the cytokine interferon-γ, supporting a role in immunity. Indeed, we demonstrate that BEST4/CA7⁺ cells generate robust CFTR-mediated fluid efflux when stimulated with bacterial diarrhea-causing toxins and find the norepinephrine-ADRA2A axis as a potential mechanism in blocking BEST4/CA7⁺ cell-mediated fluid secretion. Our observations identify a central role of BEST4/CA7⁺ cells in fluid homeostasis in response to bacterial infections.

项与 NET x α-adrenergic receptor 相关的新闻（医药）

2023-11-16

·医药观澜

爱科百发与药明康德签署战略合作协议，全面开展创新药研发合作

▎药明康德内容团队报道中国上海，2023年11月15日—上海爱科百发生物医药技术股份有限公司（以下简称“爱科百发”）与药明康德签署战略合作协议，共同宣布在创新药研发领域开展全面合作。爱科百发作为一家创新生物医药公司，针对儿科疾病、呼吸系统和肺部疾病领域未被满足的重大临床需求拥有多项新药产品布局。此次战略合作，药明康德多个业务部门将以全方位、一体化的新药研发及赋能平台为爱科百发提供符合国际标准的一站式服务。爱科百发董事长兼首席执行官邬征博士，首席运营官袁海卿博士，药明康德联席首席执行官杨青博士，副总裁、测试事业部中国区运营及业务拓展负责人许晖女士等共同出席了本次签约仪式。药明康德联席首席执行官杨青博士（左）、爱科百发董事长兼首席执行官邬征博士（右）爱科百发董事长兼CEO邬征博士表示：“爱科百发始终致力于研发具有高临床价值的创新药，很高兴此次与多年来的重要合作伙伴药明康德达成全面战略合作。双方将充分发挥各自资源优势，更好地推进药物研发工作，早日将更多创新药产品推向市场，造福大众。”药明康德联席首席执行官杨青博士表示：“此次签署战略合作协议是对双方先前成功合作的深化，是药明康德一体化、端到端服务持续赢得客户认可的又一有力体现。我们希望通过不断提升的赋能平台能力和规模建设，助力全球客户加速研发进程，早日惠及广大病患。”关于爱科百发爱科百发是一家创新生物医药公司，专注于儿童和呼吸疾病领域未被满足的重大临床需求。自2014年成立以来，公司在具有全新作用机制的创新药物研发领域拥有多项核心技术和全球专利，通过自主研发和外部引进相结合的研发模式，开发出高度差异化的丰富产品管线。核心产品爱司韦®是全球范围内首款完成三期临床试验并取得积极结果的RSV特效抗病毒药物，其新药上市申请已获NMPA受理并被纳入“优先审评审批”程序。爱司韦®也是首个纳入国家突破性治疗品种的非肿瘤新药。另一个接近商业化的产品是已获得FDA批准的多动症（ADHD）新药AZSTARYS®（中文名爱智达®），爱科百发拥有其大中华区的开发和营销权。公司还拥有数个具有同类最佳或同类首创潜力的新药正处于临床试验或临床前开发阶段。爱科百发与罗氏/基因泰克等跨国药企、美国学术机构Scripps研究所、中国科学院微生物研究所、国内外生物技术公司及跨国医疗投资机构建立了战略合作关系。公司详情，请访问网站：www.arkbiosciences.com投资者垂询：IR@arkbiosciences.com关于药明康德药明康德（股票代码：603259.SH/2359.HK）为全球生物医药行业提供一体化、端到端的新药研发和生产服务，在亚洲、欧洲、北美等地均设有运营基地。药明康德通过独特的“CRDMO”和“CTDMO”业务模式，不断降低研发门槛，助力客户提升研发效率，为患者带来更多突破性的治疗方案，服务范围涵盖化学药研发和生产、生物学研究、临床前测试和临床试验研发、细胞及基因疗法研发、测试和生产等领域。2023年，药明康德被MSCI评为ESG（环境、社会及管治）AA级。目前，公司的赋能平台正承载着来自全球30多个国家的6000多家合作伙伴的研发创新项目，致力于将更多新药、好药带给全球病患，早日实现“让天下没有难做的药，难治的病”的愿景。参考资料：[1]爱科百发与药明康德签署战略合作协议，全面开展创新药研发合作 . Retrieved Nov 16， 2023, from https://mp.weixin.qq.com/s/P3kTqcF0I9C22KWMU4ykqw本文转载自「药明康德 WuXi Biology」公众号，欢迎个人转发至朋友圈。免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。

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