The NIPA Study: A Randomized Double-blind Control Clinical Trial Naloxegol Administration to Prevent Opioids Induced Gastrointestinal Motility Disturbance in Brain Injured PAtients

Impaired gastrointestinal transit (IGT) especially constipation, is common among patients under mechanical ventilation, occurring in up to 80 % of the patients during the first week, and has been associated with worse outcome in intensive care unit (ICU). Although IGT in critically ill patients is multifactorial and some components are due to complex disease, there is increasing evidence that exogenous opioids contribute to bowel dysmotility.
Sedatives and especially opioids are largely used in the brain injured population to control intracranial pression, reduce metabolic rate, manage or prevent seizures, and improve mechanical ventilator synchrony. Therefore, brain injured patients are particularly at risk to develop IGT. The occurrence of IGT is associated with adverse outcomes in intensive care unit. Both gastric reflux and impaired peristaltic contractions are associated with ventilator-acquired pneumonia.
The actual challenge is to prevent motility disorders before it occurs. A preventive strategy could in turn reduce the occurrence of complications related to impaired gastrointestinal transit such as ventilator-acquired pneumonia, bacteremia etc. It could also reduce the complications of feed intolerance and thus reduce morbidity and mortality in ICU.
Naloxegol is a polyethylene glycol derivative of naloxol, which is a derivative of naloxone and a peripherally acting µ-opioid receptor antagonist. Contrary to naloxone, naloxegol has a very low penetration into the central nervous system, therefore it could be a relevant option for ileus prevention without the risk of impaired sedation.
The aim of our study is to assess the efficacy of the administration of naloxegol on the onset of early constipation and early ventilator-acquired pneumonia in brain injured patients receiving opioids for analgosedation.

开始日期2022-03-15

申办/合作机构

University Hospital of Brest

EUCTR2020-003687-10-BE

/ Completed临床2期IIT

Naloxegol for improving upper gastrointestinal symptoms and gastric emptying rate in patients with opioid induced constipation

开始日期2021-12-23

申办/合作机构-

100 项与纳洛塞醇相关的临床结果

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100 项与纳洛塞醇相关的专利（医药）

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项与纳洛塞醇相关的文献（医药）

2026-07-03·Expert Opinion On Drug Safety

Post-marketing safety assessment of constipation drugs: a real-world pharmacovigilance study based on FAERS database

Article

作者: Yang, Shiwei ; Zhang, Guang ; Xin, Xuezhi ; Zhang, Wenyu ; Hu, Wenqi ; Wang, Hui ; Pang, Xue

BACKGROUND:

Laxatives are widely used in the treatment of constipation, but they also have brought many adverse reactions to patients.

METHODS:

We conducted a pharmacovigilance analysis based on the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database to analyze the adverse events of six constipation drugs (linaclotide, lubiprostone, prucalopride, naloxegol, naldemedine, and plecanatide) and to search for clinically meaningful adverse reaction signals. We used disproportionality analysis as the main analysis method to detect pharmacovigilance signals, which includes Frequentist methods and Bayesian methods.

RESULTS:

Among the reports of the six drugs, more adverse reactions were reported from females than males, and the number of adverse reactions reported was higher in the group of 60-89 years. Linaclotide had the lowest proportion of serious adverse event reports (4.38%), while naldemedine had the highest proportion of serious adverse event reports (25.57%). According to the classification of system organ classification (SOC), the number of gastrointestinal adverse events (N = 8321) was the largest.

CONCLUSIONS:

The adverse reactions of constipation drugs were mainly gastrointestinal symptoms such as diarrhea, abdominal pain and abdominal distension. Linaclotide has the highest safety, and more studies are needed to analyze the cardiovascular safety of lubiprostone.

2026-06-01·Clinical Journal of Oncology Nursing

Peripherally Acting Mu-Opioid Receptor Antagonist Use in Opioid-Induced Constipation in Patients With Cancer: A Scoping Review

Article

作者: Yu, Jie

BACKGROUND:

Opioid-induced constipation (OIC) is a common and debilitating gastrointestinal side effect among adult patients with cancer receiving opioid therapy for pain management. Peripherally acting mu-opioid receptor antagonists (PAMORAs) have emerged as a promising treatment option.

OBJECTIVES:

This scoping review evaluates the current evidence regarding the efficacy and safety of three U.S. Food and Drug Administration-approved PAMORAs-naldemedine, naloxegol, and methylnaltrexone-in managing OIC in adult patients with cancer.

METHODS:

A literature search was conducted using PubMed®, CINAHL®, and Scopus® databases. Eight studies met the inclusion criteria and were analyzed.

FINDINGS:

PAMORAs effectively improved bowel movement frequency and enhanced constipation-related symptom relief and quality of life. Most adverse effects were gastrointestinal in nature but were generally mild to moderate in severity. Naloxegol and naldemedine were shown to be effective for long-term OIC management, and methylnaltrexone was effective for short-term relief.

2026-05-01·NEUROGASTROENTEROLOGY AND MOTILITY

Current Strategies and Future Perspectives in the Management of Opioid‐Induced Constipation: A Review of International and Japanese Guidelines

Review

作者: Manabe, Noriaki ; Iseki, Masako ; Ihara, Eikichi ; Camilleri, Michael ; Miwa, Hiroto ; Torii, Akira ; Yomiya, Kinomi

ABSTRACT:

Background:

Opioids are indicated for pain that occurs with cancer and other disorders that become more prevalent with aging. The most prevalent and persistent adverse effect of opioid therapy is opioid‐induced constipation (OIC). OIC impairs patient quality of life (QoL) and leads to suboptimal pain management due to medication non‐adherence. Unlike other adverse effects, OIC persists and is not associated with pharmacological tolerance, necessitating long‐term management.

Objectives:

The objective of this study is to evaluate current clinical strategies for OIC by comparing recommendations from American, European, and Japanese clinical guidelines. We reviewed the clinical evidence for the peripherally acting μ‐opioid receptor antagonist (PAMORA) naldemedine (the only PAMORA approved in Japan) and the rationale for early intervention in OIC.

Methods:

The clinical guidelines and recent clinical trial data, including the COMPOSE program (phase III clinical trials of naldemedine for OIC in patients with chronic non‐cancer pain), were reviewed to establish an evidence‐based framework for the management of chronic cancer and non‐cancer pain.

Results:

Conventional laxatives frequently provide inadequate relief as they address secondary symptoms rather than the underlying receptor‐mediated cause. PAMORAs (including naldemedine, methyl naltrexone, and naloxegol) antagonize gastrointestinal opioid receptors without compromising central analgesia. Early initiation of PAMORAs stabilizes bowel function and reduces the incidence of treatment‐related diarrhea that occurs when using conventional laxatives to treat OIC.

Conclusion:

The 2023 Japanese guidelines advocate the proactive use of the PAMORA naldemedine as a primary treatment option. This mechanism‐based early intervention model offers a promising framework for optimizing QoL and implementing effective analgesia in an aging global population.

项与纳洛塞醇相关的新闻（医药）

2026-08-03

·泉禺

止痛药王的救赎：格兰泰集团从反应停悲剧到年入18亿欧元

全球15亿人活在慢性疼痛里。每五个人中就有一个。疼痛被严重低估了。世界卫生组织直到2019年才正式将慢性疼痛认定为一种独立疾病，而非某种症状的附属品。但有一家药企，过去五十年只做一件事：止痛。它叫格兰泰（Grünenthal），总部在德国亚琛，家族企业，八十年历史，4100名员工，产品覆盖约100个国家。2025年营收18亿欧元，EBITDA连续八年增长，从1.29亿涨到5亿——翻了近三倍。它也是制药史上最严重药害事件"反应停"（沙利度胺）的开发者。从制造深渊到走向巅峰，这条路走了六十年。一、所有人都在撤退，它偏要留下来全球15亿慢性疼痛患者，但大型药企几乎全部退出了这个赛道。止痛药不赚钱。这几乎是制药界的共识。过去二十年，辉瑞、诺华、葛兰素史克等巨头相继收缩或退出疼痛研发管线。原因不复杂：疼痛机制太复杂，临床试验太难设计，投资回报率远不如肿瘤和免疫。风投的钱也跟着走了。格兰泰反其道而行。2017年起，公司把全部研发资源押在疼痛及其相邻领域——癫痫、瘙痒、神经退行性疾病。首席科学官Uli Brödl的理由很直接：我们在感觉生物学和神经元兴奋性调控上积累了几十年，这是别人没有的东西，为什么要自我设限？ CEO Gabriel Baertschi 2016年上任后定了一条战略：做疼痛领域的创新者，用非阿片类药物改写止痛药的未来。八年过去了，EBITDA从1.29亿欧元涨到5亿。在一个所有人都在撤退的赛道上逆向加注。要么是疯子，要么看到了别人没看到的东西。二、八年三倍增长，18亿欧元背后的收购引擎别人买公司是为了讲故事，格兰泰买品牌是为了算账。 2025年，格兰泰营收18亿欧元，调整后EBITDA 5亿欧元，经营性现金流从2.12亿跃升至3.09亿。自2017年以来，EBITDA增长近三倍。这组数字背后，是一台精密运转的收购引擎。八年间，格兰泰累计投入超过23亿欧元收购成熟品牌——Zomig、Crestor、Nexium、Vimovo、Movantik，以及2025年从礼来手中拿下的拉丁美洲Cialis商业化权益。每次收购的逻辑如出一辙：品牌已上市、现金流稳定、可快速整合进现有生产销售网络。 2023年，格兰泰与协和麒麟国际成立合资公司Grünenthal Meds，接手后者成熟药组合。三年内贡献3.49亿欧元营收和5700万欧元EBITDA。2026年2月，格兰泰行使期权全资收购剩余49%股权——公司M&A史上最复杂的一笔交易就此收官。负责战略的Quentin Le Masne de Chermont说得很直白：买资产时对价格很谨慎，但有强大整合能力持续改善表现。收购完成后整合团队不会在"Day One"就解散，而是继续挖掘降本空间——比如把Crestor原料药生产内化，长期贡献额外EBITDA。含协同效应，M&A贡献EBITDA达4.07亿欧元。这不是一次性故事，是可复制的模型。三、告别阿片，下一代止痛药的创新突围美国阿片危机杀死的人比越战还多。格兰泰的答案是非阿片。从1999年至今，超百万人死于阿片类药物过量。止痛不该以成瘾和死亡为代价。格兰泰管线正在回答一个问题：不用阿片，能不能有效止痛？ Qutenza（辣椒素贴片）是最成熟的非阿片止痛产品，一次贴敷提供数月疼痛缓解。2025年全球销售额1.92亿欧元，同比增长31%，治疗约12.5万名患者。美国市场7月首次月度盈利，美国由此成为格兰泰最大单一市场。更前沿的管线正在推进。NaV 1.8抑制剂——高选择性电压门控钠通道阻滞剂，2026年第一季度进入临床开发。NOP受体激动剂处于I期临床，有望成为首创级疗法，强效镇痛却不带阿片副作用。亚琛新建的寡核苷酸合成实验室将RNA疗法纳入第二条技术路线，能触达小分子无法到达的靶点。最出人意料的是tegacorat。这款选择性糖皮质受体调节剂瞄准的不是疼痛，而是杜氏肌营养不良症（DMD）——每5000个男婴中有一人患此致命遗传病。现有标准疗法皮质类固醇副作用严重，tegacorat有望在保持抗炎效力的同时大幅降低副作用。II期临床2026年启动。杜氏肌营养不良父母项目创始人Pat Furlong说："把疾病稳定在现在的位置，对患者和父母就是整个世界。" 四、厄瓜多尔的工厂，全球供应链的降维打击别人把工厂开在瑞士，格兰泰把新工厂开在厄瓜多尔。 2025年，格兰泰厄瓜多尔基多工厂获欧盟监管批准，商业化生产Vimovo。这是公司历史上第一次全球产品在非欧洲工厂生产。基多工厂产能3亿片/年，新增60台设备，翻倍扩建厂区，预计每年贡献1000万欧元毛利率改善。基多也是厄瓜多尔唯一获欧盟认证的生产基地——合规壁垒上先拔头筹。这背后是"垂直整合"。格兰泰在全球有5个生产基地——德国、意大利、瑞士、智利、厄瓜多尔，47个国籍的2000多名运营人员。每次收购品牌后，团队系统评估是否将生产转入自有工厂。内化生产降本、强化质量管控、保供应安全。 Global Operations五年战略周期GO2025交出亮眼成绩单：贡献EBITDA 1.108亿欧元，M&A年化回报率15.6%——是欧盟药企基准7.4%的两倍多。2025年生产1.3亿片药，零损失工时事故，零关键偏差。2026年将启动GO2030，聚焦成本领导力、整合卓越和安全质量标杆。五、反应停六十年，一个还不清的债过去无法撤销。但改善受影响者现在和未来的生活条件，是我们的责任。 1957年，格兰泰以"反应停"（Contergan）为商品名推出沙利度胺，作为镇静剂在40多个国家销售，广告宣称"安全无毒，孕妇儿童均可服用"。1961年，澳大利亚医生在《柳叶刀》发文，将海豹肢畸形与孕期服用反应停联系起来。全球超过一万名孩子带着严重肢体缺陷出生。产品紧急撤市，但伤害已无法挽回。这是制药工业史上最黑暗的章节之一。格兰泰就是那个执笔的人。六十多年过去了。受影响者如今大多六十几岁，面临衰老带来的新挑战。格兰泰成立了"沙利度胺受影响人群支持基金会"，自2012年以来提供超过5300项个人援助措施，覆盖到2025年底的1000名个体。基金会重点已从居家改造转向移动出行——自适应车辆、电动轮椅、定制辅助设备，让这些人能走出家门、参与社区。格兰泰还与德国联邦沙利度胺受影响者协会共建"知识之地"数字平台，让这段历史可见、可及。 2021年，公司股东Michael Wirtz家族正式向受影响者道歉。5300项援助、1000个个体、二十年的社区基金——用一个还不清的债在赎罪。六、从ESG金奖到十万棵树，家族企业的长期主义上市公司看季度，家族企业看世代。格兰泰没上市，不向华尔街的季度数字表演负责。这份从容让它能投资十年后才见效的管线，能在所有人退出时坚守疼痛领域，能为六十年前的过错持续偿付。 ESG上的表现是长期投入的复利。2025年，MSCI连续第二年给出(p) AA评级，EcoVadis金章将其列入全球前5%，Sustainalytics认证为低ESG风险。SBTi批准其近期气候目标，与1.5°C温控一致。所有生产基地100%使用可再生电力，Scope 1和2排放自2020年下降43%，研究实验室全部通过MyGreen Lab认证。2025年在塞内加尔和肯尼亚/坦桑尼亚种下10万棵树，完成首个项目周期，十年内有望达100万棵。员工层面，25个国家获Great Place to Work认证，88%受访者说格兰泰是个好雇主。2025年全球志愿服务超4300小时。这些成绩不是某一年突击做的。家族企业的好处就在这里——没有人逼你证明下季度会比这季度好。格兰泰的未来，藏在它的过去里。八十年前从亚琛起步，五十年前专注止痛，六十年前犯下大错，八年前开启转型。每一步走得慢，但每一步都留了痕迹。 18亿欧元营收，5亿欧元EBITDA，15亿慢性疼痛患者，100个国家，4100人。 A World Free of Pain 一个没有疼痛的世界。听起来天真。但已经有人为它走了八十年。

并购

2026-03-02

·PRNewswire

Grünenthal takes full ownership of Grünenthal Meds, the joint venture established with Kyowa Kirin for its established medicines brands

Grünenthal acquired Kyowa Kirin International's 49% stake in 'Grünenthal Meds', a joint venture formed in 2023 to market the established medicines portfolio from Kyowa Kirin International. Through this acquisition, Grünenthal assumes the sole responsibility of a portfolio comprising 12 brands across six therapeutic areas and >60 markets. AACHEN, Germany, March 2, 2026 /PRNewswire/ -- Grünenthal today announced that it has acquired Kyowa Kirin International's 49% stake in 'Grünenthal Meds', taking full ownership of the company formed through a joint venture and its portfolio of established medicines. 'Grünenthal Meds' was created in 2023 as a joint venture between Grünenthal (51%) and Kyowa Kirin International (49%), the EMEA business of the Japanese-based global specialty pharmaceutical company. Over the past three years, the joint venture operated as a separate entity with eight affiliates, managing a growing €170 million portfolio of 12 established brands across six therapeutic areas and more than 60 markets. Key products included Abstral® and PecFent® (Fentanyl) for breakthrough cancer pain, Moventig® (Naloxegol) for opioid-induced constipation and Adcal-D3® (calcium and vitamin D3) for osteoporosis. "Thanks to the outstanding expertise and commitment of our teams in Grünenthal and Grünenthal Meds, we were able to manage this complex portfolio across regions, generate growth, and create synergies with our infrastructure – all while executing a staggered integration approach," said Gabriel Baertschi, Chief Executive Officer of Grünenthal. "The integration of 'Grünenthal Meds' confirms our leading capabilities in deal execution and integration and successfully concludes one of the most complex undertakings of our M&A journey, which stretched far beyond a merger or asset deal." The ongoing integration of 'Grünenthal Meds' includes the transfer of more than 200 marketing authorisations, approximately 150 product-country combinations, and several tech transfers in close alignment with a broad landscape of partners and contract manufacturing organisations. Grünenthal expects to complete the integration by June 2026. At this point, Grünenthal will commercialise the 'Grünenthal Meds' portfolio through Grünenthal affiliates in major European markets and via international partners in additional territories. The acquisition of 'Grünenthal Meds' is based on an option agreed with Kyowa Kirin International at the beginning of the joint venture collaboration. The transaction supports Grünenthal's long-term growth strategy. Since 2017, Grünenthal has closed successful acquisitions with a total expected deal value of more than €2.3 billion, strengthening and diversifying its portfolio while leveraging synergies across manufacturing, supply chain, logistics, and commercial operations. About Grünenthal Grünenthal is a global leader in pain management and related diseases. As a science-based, fully integrated pharmaceutical company, we have a long track record of bringing innovative treatments and state-of-the-art technologies to patients worldwide. Our purpose is to change lives for the better – and innovation is our passion. We focus all our activities and efforts on working towards our vision of a World Free of Pain. Grünenthal is headquartered in Aachen, Germany, and has affiliates in 28 countries across Europe, Latin America, and the U.S. Our products are available in approx. 100 countries. In 2024, Grünenthal employed around 4,300 people and achieved revenues of €1.8 billion. More information: Follow us on LinkedIn & Instagram For further information, please contact: Maren Thurow, Head Global Communications at Grünenthal [email protected] SOURCE Grunenthal Group 21% more press release views with Request a Demo

并购

2025-12-27

·今日头条

11文一览"肠-脑"研究转化新进展，中国成果亮眼！｜热心肠日报

该篇日报由R·base创作生成，人工审核校对。袁勇贵/张学丽/郑啸等：牛磺胆酸连接菌群紊乱与抑郁症 Advanced Science——[14.1] ① 研究背景与设计：本研究针对抑郁症代谢特征与病理机制不清的问题，通过多中心临床队列结合小鼠模型，探究胆汁酸谱系改变与抑郁行为及脑功能连接的因果关联。② 核心发现：研究确立了血清牛磺胆酸（TCA）为抑郁症潜在诊断标志物，揭示了其通过激活海马S1PR2受体诱发神经炎症并损害神经发生的致病机制。③ 临床血清代谢特征：基于五个独立临床队列分析发现，抑郁症患者血清TCA水平显著升高，且抗抑郁治疗后TCA水平随HAMD评分改善而同步下降。④ 菌群移植与致病机制：患者粪菌移植导致受体小鼠海马TCA积聚及抑郁样行为，外源性补充TCA可激活小胶质细胞并抑制神经发生，该效应可被S1PR2拮抗剂阻断。⑤ 神经影像关联分析：功能磁共振显示血清TCA水平与海马亚区（如左侧旁下托）跟全脑（如右侧壳核）的功能连接强度呈负相关，联合诊断模型AUC高达0.88。⑥ 临床转化与治疗意义：本研究证实TCA是连接肠道菌群紊乱与大脑海马功能异常的关键介质，提示调控TCA代谢或靶向S1PR2通路是抑郁症治疗的新策略。【原文信息】 Taurocholic Acid Is Associated With Disturbed Functional Connectivity in the Hippocampus of Patients With Depression 2025-12-23 , doi: 10.1002/advs.202508693 张建成/袁世荧等：肠道γδ T17细胞入侵大脑损害线粒体致抑郁 Journal of Neuroinflammation——[10.1] ① 研究背景与设计：本研究利用慢性束缚应激（CRS）小鼠模型，结合Kaede光转换追踪及条件性基因敲除技术，探究肠-免疫-脑轴在抑郁症发病中的作用。② 核心发现：肠道CD8α+ γδ T17细胞迁移至脑部并通过IL-17A抑制海马线粒体自噬引发抑郁的机制，R-氯胺酮（Arketamine）可阻断此病理过程。③ 免疫细胞脑部迁移：CRS导致肠道屏障受损，促使小肠CD8α+ γδ T17细胞经循环迁移至脑膜和脑实质，成为脑内IL-17A的主要来源。④ 菌群驱动病理机制：CRS诱导的肠道菌群失调是细胞迁移的驱动力，将CRS小鼠粪便移植给抗生素处理小鼠可重现抑郁行为及γδ T细胞的脑部浸润。⑤ 线粒体自噬受阻：海马中升高的IL-17A抑制PINK1/Parkin信号通路，导致线粒体自噬受损（p62累积、LC3B-II/I降低）、ATP减少及突触超微结构损伤。⑥ 药物干预与修复：R-氯胺酮通过改善菌群失调，减少γδ T细胞脑部迁移及IL-17A水平，恢复PINK1/Parkin介导的线粒体自噬并缓解抑郁。【原文信息】 Intestinal γδ T17-IL-17A signaling disrupts hippocampal mitophagy in stress-induced depression and is restored by arketamine 2025-12-18 , doi: 10.1186/s12974-025-03656-4 林静娴/赖信志等：戈氏副拟杆菌经肠-脑轴抑制炎症缓解帕金森病 Journal of Advanced Research——[13] ① 研究背景与设计：本研究针对帕金森病（PD）前驱期干预难题，利用LRRK2 G2019S突变小鼠模型，结合空间转录组及单细胞测序，探究口服戈氏副拟杆菌（P. goldsteinii）对PD病理进程的阻断作用。② 核心发现与意义：研究发现P. goldsteinii能通过调节肠-脑轴改善运动障碍和多巴胺能神经元丢失，揭示了其通过非经典 IL-12 信号通路发挥神经保护作用的全新机制。③ 菌群驱动疾病进展：无菌条件可减轻LRRK2突变小鼠的运动缺陷及神经退行性病变，证实肠道菌群是驱动该模型PD表型的关键。④ 中枢抗炎神经保护：P. goldsteinii定植能特异性抑制脑内Tlr4/NF-κB炎症级联反应及小胶质细胞活化，减少α-突触核蛋白聚集并挽救多巴胺能神经元。⑤ 非经典信号介导：该菌通过提升全身IL-12水平激活神经元IL-12Rβ2，启动非经典神经营养通路（而非STAT4信号），实现远程神经保护。⑥ 特异性免疫重塑：在肠道内，P. goldsteinii下调Tlr4信号并促进抗炎性 CD4+CD8αα+ T细胞扩增，逆转了LRRK2突变导致的免疫失衡。⑦ 线粒体与屏障修复：该菌还通过增强肠上皮细胞线粒体氧化磷酸化及上调紧密连接基因，修复肠道生物能量代谢与物理屏障，从源头阻断病理传播。【原文信息】 Parabacteroides goldsteinii mitigates parkinsonism in LRRK2 mutant mice by reducing neuroinflammation through Gut-Brain axis 2025-12-23 , doi: 10.1016/j.jare.2025.12.028 曹鹏/王胜/张智/柴小青等NC：吗啡诱导便秘的脑-肠神经通路 Nature Communications——[15.7] ① 研究背景与设计：本研究利用雄性小鼠模型结合病毒示踪及微内窥镜钙成像技术，解析吗啡诱导便秘的中枢神经回路机制。② 核心发现与意义：研究揭示了PVNGlu→DMVAch→小肠神经回路，证实该中枢通路下调是导致吗啡致便秘的关键机制。③ 神经投射机制：解剖学证据显示，迷走神经背核（DMV）乙酰胆碱能神经元（DMVAch）直接投射至小肠肌层，其光遗传学激活能显著逆转吗啡引起的肠动力抑制。④ 中枢抑制通路：吗啡作用于下丘脑室旁核（PVN）谷氨酸能神经元（PVNGlu）的μ-阿片受体（MOR），通过降低NMDA受体介导的紧张性电流，抑制DMVAch活性。⑤ 功能挽救验证：在PVNGlu中特异性敲降Oprm1基因或化学遗传激活该回路，均能有效缓解吗啡诱导的便秘症状。⑥ 中枢外周协同：实验证实外周MOR拮抗剂Naloxegol仅能部分缓解便秘，强调了中枢PVN-DMV回路在调节小肠运动中的决定性作用。⑦ 总结与展望：本研究确立了脑-肠轴在阿片类药物副作用中的核心地位，为开发治疗阿片致便秘的新型神经调控疗法提供了理论依据。【原文信息】 A brain-to-small intestine circuit mediates morphine-induced constipation in male mice 2025-12-23 , doi: 10.1038/s41467-025-67765-7 脑-肠神经对话调控胃肠功能与疾病（综述） Physiological Reviews——[28.7] ① 总体概述：本文综述了中枢神经系统（CNS）对胃肠（GI）功能的复杂调控网络，强调脑干及高位中枢如何通过自主神经通路与肠神经系统（ENS）协同作用以维持稳态。② ENS半自主性：ENS依靠肌间和黏膜下神经丛能半自主地控制胃肠运动与分泌，但其功能仍受外在交感与副交感神经的精细调节且各肠段受控度不同。③ 交感神经抑制：交感神经主要负责血管收缩及括约肌张力调节，并通过突触前抑制机制减弱肠道运动，其在远端肠道的特殊分布有助于调控内容物的传输与留存。④ 迷走双向调节：副交感神经（迷走神经）对胃肠运动和分泌具有兴奋与抑制的双重作用，并通过胆碱能抗炎通路激活巨噬细胞上的α7烟碱受体来抑制肠道炎症。⑤ 脑干信号整合：孤束核（NTS）和迷走神经背核（DMV）是脑干整合核心，负责汇聚来自内脏的感觉传入与高位中枢的下行指令，直接调控迷走神经传出信号。⑥ 菌群神经互作：肠道微生物通过代谢产物（如SCFAs）直接刺激肠内分泌细胞或激活迷走传入纤维，进而通过神经回路调节宿主的摄食、情绪及运动行为。⑦ 高位中枢调控：压力通过杏仁核、终纹床核及下丘脑室旁核等边缘系统与脑干的连接影响胃肠功能，这些区域的连接异常常导致内脏高敏感性或功能性胃肠病。⑧ 神经可塑性改变：迷走神经回路具有高度可塑性，高脂饮食或肥胖可改变传入神经敏感性及DMV神经元兴奋性，这种神经适应性失效是引发代谢及胃肠疾病的关键。【原文信息】 Central Control of Gastrointestinal Functions in Health and Disease 2025-12-23 , doi: 10.1152/physrev.00010.2025 肠菌分子模拟触发中枢自身免疫神经炎症 Gut Microbes——[11] ① 模型构建与设计：构建表达髓鞘抗原MOG35-55的工程化沙门氏菌（Sal-MOG）和大肠杆菌，利用TCRMOG小鼠探究肠道抗原驱动神经炎症的机制。② 核心结论：肠道细菌表达自身抗原足以在肠系膜淋巴结激活特异性CD4+ T细胞，进而驱动中枢神经系统自身免疫病。③ 抗原特异性验证：体外实验证实，表达MOG35-55的细菌能特异性激活MOG反应性T细胞，而表达OVA对照抗原的菌株无此效应。④ 加速疾病进程：在SPF小鼠中，定植Sal-MOG不仅导致运动受损，还在百日咳毒素诱导下显著加速实验性自身免疫性脑脊髓炎（EAE）。⑤ 诱发自发病变：无菌小鼠单定植Sal-MOG可诱发自发性疾病，伴随肠系膜淋巴结中T细胞早期激活标志物Cd69上调及B细胞产生自身抗体。⑥ 载体效应差异：表达同种抗原的大肠杆菌虽致病但病情较轻且无自身抗体，表明细菌载体的炎性特性显著调节免疫反应强度。⑦ 研究科学意义：本研究确立了“分子模拟”经由肠道启动中枢自身免疫的确切路径，为靶向微生物治疗多发性硬化症提供新思路。【原文信息】 Antigen-specific activation of gut immune cells drives autoimmune neuroinflammation 2025-12-24 , doi: 10.1080/19490976.2025.2601430 AI多组学"算"出肠脑互作障碍疾病亚型 Gut Microbes——[11] ① 多组学聚类研究设计：本研究整合了下消化道肠-脑互作障碍（DGBI）患者与健康对照的临床症状、肠道宏基因组及代谢组数据，采用无监督机器学习探索疾病亚型。② 核心发现：研究证实基于Rome IV标准的诊断缺乏生物学特异性，并通过多模态聚类识别出具有独特氨代谢及转运通路异常的稳定DGBI亚群。③ 症状表型的独立性：症状聚类显示心理负担与胃肠道症状严重程度并不完全耦合，识别出“脑主导”与“肠主导”的不同患者亚群，且部分健康对照也存在高心理症状。④ 生物学特征的局限：单一维度的生物学数据聚类（如微生物组或代谢组）无法区分临床诊断类型，提示仅靠单一生物标志物难以捕捉DGBI的复杂病理。⑤ 识别高痛觉生物亚型：整合分析发现“肠主导高痛觉”亚型表现为微生物氮通量降低及宿主尿素循环受损，提示氨代谢异常可能驱动内脏高敏感性。⑥ 解析菌群失调机制：另一“菌群失调”亚型特征为预期物种丰富度降低及ABC转运体通路富集，暗示糖代谢紊乱及机会致病菌增殖。⑦ 精准分型临床启示：本研究挑战了现有基于症状的分类体系，提出整合多组学特征的精准分型策略，为DGBI的个性化治疗提供了潜在的新靶点。【原文信息】 Integrated multi-omic and symptom clustering reveals lower-gastrointestinal disorders of gut-brain interaction heterogeneity 2025-12-23 , doi: 10.1080/19490976.2025.2604871 幽门螺杆菌通过炎症机制，独立驱动帕金森病样神经退行 Journal of Neuroinflammation——[10.1] ① 背景与实验设计：本研究利用小鼠模型结合幽门螺杆菌（H. pylori）慢性感染与α-突触核蛋白原纤维颅内注射，探究病原体感染对帕金森病病理及神经变性的影响。② 核心发现与价值：研究证实H. pylori感染通过炎症途径独立驱动黑质多巴胺能神经元丢失，揭示了非α-突触核蛋白聚集依赖的神经退行性病变新机制。③ 炎症驱动机制：慢性H. pylori感染诱导胃部CD3+ T细胞浸润及血浆IFN-γ水平持续升高，导致黑质星形胶质细胞活化及神经元死亡。④ 治疗逆转效应：三联抗生素疗法可有效清除感染并逆转全身炎症及神经元丢失，但黑质区域的星形胶质细胞活化状态在清除感染后仍持续存在。⑤ 双重打击评估：在α-突触核蛋白原纤维诱导的模型中，H. pylori感染并未进一步加剧α-突触核蛋白的病理扩散或加重神经元死亡，表明二者致病路径平行且独立。⑥ 环境风险提示：研究结果支持H. pylori作为环境风险因子，通过外周-中枢炎症轴促进帕金森病相关神经退行，强调了早期清除感染的潜在神经保护价值【原文信息】 Helicobacter pylori infection and α-synuclein pathology drive parallel neurodegenerative pathways in the substantia nigra 2025-12-22 , doi: 10.1186/s12974-025-03596-z 27年数据揭示膳食硝酸盐来源决定痴呆风险 Alzheimer's and Dementia——[11.1] ① 研究背景与设计：本研究基于丹麦DCH队列，纳入54,804名受试者并随访27年，解析植物、动物及自来水来源的膳食硝酸盐和亚硝酸盐摄入与痴呆发病风险的关联。② 核心发现与意义：确立了硝酸盐神经效应的“来源依赖性”，证实植物源性摄入具神经保护作用，而动物源性和自来水来源则增加风险，修正了既往单一维度的健康假说。③ 植物源性保护作用：高植物源性（尤以蔬菜为主）硝酸盐摄入与全因痴呆风险降低约10%显著相关，且对早发性痴呆保护效应更强（风险降低31%-39%）。④ 动物源性潜在危害：高水平天然动物源性硝酸盐及加工肉类添加剂摄入均与痴呆高发显著相关，其中天然动物源性摄入致早发性痴呆风险激增73%。⑤ 饮用水风险关联：自来水硝酸盐摄入与痴呆风险呈非线性正相关，即便浓度低于现行监管限值，高摄入组痴呆发病率仍较对照组升高14%。⑥ 抗氧化剂交互效应：植物源性硝酸盐的保护作用在低维生素C或多酚摄入人群中更为显著，提示其可能通过改善内皮功能提供独立的血管保护益处。【原文信息】 Source-specific nitrate intake and incident dementia in the Danish Diet, Cancer and Health Study 2025-12-19 , doi: 10.1002/alz.70995 西洋参提取物改善突触韧性，或可延缓认知衰老 Alzheimer's and Dementia——[11.1] ① 研究背景与设计：本研究针对衰老相关的蛋白质稳态失衡问题，利用大鼠海马脑片培养及老年Fischer大鼠模型，评估了西洋参（PanQ）等植物提取物对自噬溶酶体通路（ALP）的调节作用。② 核心发现与意义：研究确立了PanQ通过特异性增强溶酶体酶活性及突触韧性来逆转认知衰老，揭示了其作为神经退行性疾病早期膳食干预策略的科学价值。③ 提取物筛选与机制：在对比多种提取物后，发现PanQ与假马齿苋能最显著地提升活性组织蛋白酶B（CatB）水平，且该酶活性提升与突触蛋白（GluA1）及自噬标记物LC3-II的表达增强呈强正相关。④ 突触韧性验证：在氯喹诱导的溶酶体压力及突触病变模型中，PanQ预处理通过维持CatB介导的蛋白降解能力，有效阻止了突触后GluA1及突触前突触素（SNP）的病理性丢失。⑤ 体内认知改善：在20月龄老年大鼠的被动回避实验中，PanQ膳食补充显著改善了与年龄相关的学习记忆缺陷，蛋白质组学分析证实其作用涉及自噬调节与蛋白质泛素化通路的激活。【原文信息】 Ginseng extract improves synaptic resiliency: A key factor for healthy cognitive aging 2025-12-19 , doi: 10.1002/alz.70818 瑞典25年研究：多吃高脂奶酪或可降低痴呆风险 Neurology——[8.5] ① 研究背景与设计：本研究基于瑞典Malmö饮食与癌症队列，对27,670名参与者进行25年随访，探究不同脂肪含量乳制品与痴呆风险的关联。② 核心发现：每日摄入高脂奶酪（≥50g）或高脂奶油（≥20g）与全因痴呆风险分别降低13%和16%显著相关。③ 痴呆亚型特异性：高脂奶酪摄入可使血管性痴呆风险降低29%，且在APOE ε4非携带者中显示出针对阿尔茨海默病的显著保护作用。④ 不同基质效应差异：与奶酪和奶油的保护作用相反，极高量的黄油摄入（≥40g/天）与阿尔茨海默病风险增加显著相关。⑤ 低脂与牛奶关联：低脂乳制品、普通牛奶（无论高低脂）及发酵乳摄入与全因痴呆风险无显著关联，提示乳制品基质的关键作用。⑥ 食物替代风险评估：等量替代分析显示，若用红肉、加工肉类或全脂牛奶替代高脂奶酪与奶油，全因痴呆发生风险将显著增加。⑦ 研究局限与启示：尽管观察性设计无法确立因果，结果有力挑战了传统低脂饮食建议，提示富含特定脂肪的乳制品可能具有神经保护潜力。【原文信息】 High- and Low-Fat Dairy Consumption and Long-Term Risk of Dementia: Evidence From a 25-Year Prospective Cohort Study 2025-12-17 , doi: 10.1212/WNL.0000000000214343

100 项与纳洛塞醇相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10375	-	A06AH03	DB09049

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
便秘	加拿大	Knight Therapeutics, Inc.	2015-08-27
阿片类药物引起的便秘	美国	Averitas Pharma, Inc.	2014-09-16

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
危重病	临床3期	美国	AstraZeneca PLC	2017-05-01
癌症疼痛	临床3期	美国	AstraZeneca PLC	2011-03-01
癌症疼痛	临床3期	澳大利亚	AstraZeneca PLC	2011-03-01
癌症疼痛	临床3期	比利时	AstraZeneca PLC	2011-03-01
癌症疼痛	临床3期	克罗地亚	AstraZeneca PLC	2011-03-01
癌症疼痛	临床3期	捷克	AstraZeneca PLC	2011-03-01
癌症疼痛	临床3期	德国	AstraZeneca PLC	2011-03-01
癌症疼痛	临床3期	匈牙利	AstraZeneca PLC	2011-03-01
癌症疼痛	临床3期	斯洛伐克	AstraZeneca PLC	2011-03-01
癌症疼痛	临床3期	西班牙	AstraZeneca PLC	2011-03-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04433390 (Pubmed \| Anaesth Crit Care Pain Med)	临床3期	术后肠梗阻	299	Naloxegol 12.5 mg followed by Naloxegol 25 mg	餘窪壓鬱蓋淵繭簾鬱獵(遞醖糧製夢顧製鹽觸膚) = 衊獵鹽觸網餘獵餘顧淵鬱夢網廠簾糧憲觸網鑰 (蓋蓋鑰鑰網遞夢鏇鹽糧, 69.3 ~ 93.5)	不佳	2025-04-01
				Placebo	餘窪壓鬱蓋淵繭簾鬱獵(遞醖糧製夢顧製鹽觸膚) = 製憲膚顧願淵餘簾顧夢鬱夢網廠簾糧憲觸網鑰 (蓋蓋鑰鑰網遞夢鏇鹽糧, 70.0 ~ 95.8)
NCT03523520 (CTgov)	临床4期	阿片类药物引起的便秘	15	Methylnaltrexone Bromide 150 mg Oral Tablet (Methylnaltrexone Oral Tablets)	網餘選網簾壓壓餘顧網 = 鏇醖積鹹積鑰壓願餘繭願蓋窪餘繭築鹹選鏇夢 (衊糧鹹廠願鬱艱襯壓鬱, 憲範夢餘遞醖積積鬱膚 ~ 構醖窪構繭夢衊艱網鹽) 更多	-	2024-09-19
				Methylnaltrexone Bromide 12 MG/0.6 ML Subcutaneous Solution [RELISTOR]_#1 (Methylnaltrexone Subcutaneous Injection)	網餘選網簾壓壓餘顧網 = 願襯鏇廠製願網窪糧鑰願蓋窪餘繭築鹹選鏇夢 (衊糧鹹廠願鬱艱襯壓鬱, 艱醖醖廠選壓淵鹽獵齋 ~ 壓膚鹽鬱範觸夢襯膚醖) 更多
NCT03235739 (CTgov)	临床4期	术后疼痛	136	Placebo	鹹築簾網膚窪積廠願廠(夢艱鏇積範鏇願糧積簾) = 製鑰鏇襯鏇鏇壓積願餘壓膚憲鏇糧齋簾構廠窪 (憲膚壓壓鏇網築獵鏇顧, 構築鬱顧繭積蓋鏇艱範 ~ 淵鑰遞淵遞選顧齋鑰觸) 更多	-	2023-09-05
NCT02977286 (CTgov)	临床4期	便秘	12	Polyethylene Glycols+Magnesium Citrate Oral Liquid Product+Bisacodyl 10 mg Suppository+Docusate Sodium 100 Mg oral capsule [Colace]+Naloxegol Oral Tablet+Senna 217 Mg Oral Tablet+Methylnaltrexone (Naloxegol Oral Tablet)	範艱簾願獵獵遞夢襯鹹(餘糧蓋簾醖襯製淵積蓋) = 觸夢簾觸鹽鏇範鹹願顧壓選築憲襯鬱遞範膚廠 (構憲構蓋築築壓顧積壓, 25) 更多	-	2023-02-16
				Placebo Oral Tablet+Magnesium Citrate Oral Liquid Product+Bisacodyl 10 mg Suppository+Docusate Sodium 100 Mg oral capsule [Colace]+Senna 217 Mg Oral Tablet+Methylnaltrexone (Placebo Oral Tablet)	範艱簾願獵獵遞夢襯鹹(餘糧蓋簾醖襯製淵積蓋) = 窪鑰築膚齋憲餘夢製鹹壓選築憲襯鬱遞範膚廠 (構憲構蓋築築壓顧積壓, 25) 更多
NCT03638440 (NACASY, ESMO2020)	N/A	阿片类药物引起的便秘	-	Naloxegol	壓範遞鏇蓋餘觸膚獵鬱(膚範選範製顧鹽鏇遞築) = grade 1-2 鏇顧製鏇願遞積構構齋 (範艱壓鑰襯鹽膚選衊憲 ) 更多	-	2020-09-17
ESMO2020	N/A	阿片类药物引起的便秘	126	Naloxegol	醖壓廠觸廠鹽網醖簾選(蓋壓製壓獵鏇簾襯廠齋) = 28 adverse reactions, mainly gastrointestinal, were observed in 15.1% of the patients (19/126), being 75% (21) mild, 17.9% (5) moderate and 7.1% (2) severe. Most adverse reactions (67.9%) appeared the first 15 days of treatment. 餘積餘醖觸顧淵遞選鏇 (構構繭餘壓夢淵製餘簾 )	积极	2020-09-17
ASCO2020	N/A	阿片类药物引起的便秘	126	Naloxegol 25 mg/day	獵齋壓網積窪製餘網願(憲遞願膚醖鹹觸鏇鬱製) = A total of 28 adverse reactions mainly gastrointestinal were observed in 15.1% of the patients (19/126), 75% (21) mild, 17.9% (5) moderate and 7.1% (2) severe. Most adverse reactions (67.9%) were observed the first 15 days of treatment with naloxegol. 觸窪鏇觸願築顧築衊顧 (鹹廠鏇壓醖齋壓糧鬱選 )	积极	2020-05-25
				Naloxegol 12.5 mg/day
ESMO2019	N/A	阿片类药物引起的便秘	126	Naloxegol 12.5mg/day	蓋糧餘艱壓糧齋獵淵餘(遞獵網顧夢範繭獵淵繭) = A total of 24 adverse reactions appeared in 13.5% of the patients (17/126) 餘齋鑰鏇簾築範糧憲窪 (醖蓋廠艱範積簾餘鑰艱 )	积极	2019-09-28
				Naloxegol 25mg/day
NCT02946580 (CTgov)	临床4期	便秘	53	naloxegol (MOVANTIK™ (Naloxegol))	夢遞鹹鬱鏇壓餘醖醖齋(繭範鑰鏇繭餘餘膚繭淵) = 簾獵鹽鹽積製壓選襯鏇鏇製壓糧餘築觸衊糧蓋 (廠窪艱構夢醖網膚顧壓, 廠壓積積鹽襯鏇繭築網 ~ 膚觸願積簾憲衊獵繭鬱) 更多	-	2019-09-10
				sugar pill (Sugar Pill)	夢遞鹹鬱鏇壓餘醖醖齋(繭範鑰鏇繭餘餘膚繭淵) = 醖願鬱鹹築膚鑰鬱築醖鏇製壓糧餘築觸衊糧蓋 (廠窪艱構夢醖網膚顧壓, 鬱構膚艱觸構襯觸製夢 ~ 淵齋窪製膚網廠簾餘餘) 更多
NCT02839889 (CTgov)	临床4期	癌症疼痛 \| 疼痛 \| 阿片类药物引起的便秘 ... 更多	12	Placebo (Placebo)	糧窪鹹築壓夢鹹構艱廠(製艱糧糧鹹築積鬱壓築) = 遞觸選鹽襯衊獵願繭製壓鹹顧鑰餘糧蓋衊築夢 (觸願簾鏇艱衊齋獵顧簾, 醖窪構構醖壓餘構鏇築 ~ 願願繭鏇壓範獵獵艱憲) 更多	-	2019-03-05
				Naloxegol (Naloxegol)	糧窪鹹築壓夢鹹構艱廠(製艱糧糧鹹築積鬱壓築) = 鏇願鹽顧鬱衊廠積範鑰壓鹹顧鑰餘糧蓋衊築夢 (觸願簾鏇艱衊齋獵顧簾, 獵構築觸廠艱鏇夢窪艱 ~ 構糧鏇夢鑰觸獵淵醖願) 更多