Current Opinion in Pharmacology最新文献

英文中文

Ivermectin and non-parasitic disorders: An update 伊维菌素和非寄生虫疾病：最新进展。

IF 4.2 3区医学 Q1 PHARMACOLOGY & PHARMACY

Current Opinion in Pharmacology

Pub Date : 2025-09-16 DOI: 10.1016/j.coph.2025.102574

Behdad Seyyedabadi , Shabnam Babataheri , Marziyeh Naseri , Ismail Laher , Hamid Soraya

Ivermectin, a broad-spectrum anti-parasitic agent, demonstrates potential therapeutic benefits in treating non-parasitic ailments, particularly in neurological, respiratory, inflammatory, dermal, cardiovascular, and neoplastic disorders. For instance, ivermectin targets both DNA and RNA viruses, inhibits angiogenesis, and has anti-cancer properties, which result from inhibiting RNA helicase, inducing mitochondrial dysfunction, apoptosis, necrosis, and autophagy, as well as promoting oxidative stress. While the precise neurological impacts of ivermectin are not fully understood, it also has anticonvulsant properties in rats. Recent discoveries have revealed the neuroprotective effects of ivermectin in cerebral ischemia/reperfusion and Alzheimer's disease. Although there is limited research on the influence of ivermectin on the cardiovascular system, some studies have reported cardioprotective effects of ivermectin. However, a recent study suggested that ivermectin pre-treatment may have detrimental effects on myocardial ischemia. Consequently, numerous questions regarding the therapeutic/adverse effects of ivermectin remain unanswered and necessitate further investigation. We review the effects of ivermectin in non-parasitic diseases with an emphasis on current research in this field.

伊维菌素是一种广谱抗寄生虫剂，在治疗非寄生虫疾病，特别是神经、呼吸、炎症、皮肤、心血管和肿瘤疾病方面显示出潜在的治疗益处。例如，伊维菌素针对DNA和RNA病毒，抑制血管生成，并具有抗癌特性，这是由于抑制RNA解旋酶，诱导线粒体功能障碍，细胞凋亡，坏死和自噬，以及促进氧化应激。虽然伊维菌素对神经系统的确切影响尚不完全清楚，但它在大鼠身上也有抗惊厥的特性。最近的研究发现伊维菌素在脑缺血/再灌注和阿尔茨海默病中具有神经保护作用。尽管关于伊维菌素对心血管系统影响的研究有限，但一些研究报道了伊维菌素的心脏保护作用。然而，最近的一项研究表明，伊维菌素预处理可能对心肌缺血有不利影响。因此，关于伊维菌素的治疗/不良反应的许多问题仍然没有答案，需要进一步调查。我们回顾了伊维菌素在非寄生虫病中的作用，重点介绍了该领域的研究现状。

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引用次数: 0

Modulating neuroinflammation through electroacupuncture: Mechanistic insights and pharmacological synergies 通过电针调节神经炎症：机制见解和药理学协同作用

IF 4.2 3区医学 Q1 PHARMACOLOGY & PHARMACY

Current Opinion in Pharmacology

Pub Date : 2025-09-04 DOI: 10.1016/j.coph.2025.102564

Salvador Quiroz-González , Erika Elizabeth Rodríguez-Torres , Ismael Jiménez-Estrada

Neuroinflammation plays a central role in the pathogenesis of numerous neurological and neurodegenerative diseases, driven by complex interactions among glial activation, cytokine release, blood–brain barrier (BBB) dysfunction, and autonomic dysregulation. While pharmacological therapies targeting inflammatory mediators show promise, their efficacy is often limited by poor BBB permeability and systemic side effects. Electroacupuncture (EA), a neuromodulatory technique that combines acupuncture with electrical stimulation, has emerged as a promising adjunctive intervention for modulating neuroimmune dynamics. EA activates defined somatosensory afferents and transmits signals to key autonomic and limbic nuclei, including the brainstem and hypothalamus, which regulate immune responses. At the molecular level, EA suppresses pro-inflammatory pathways such as TLR4/NF- κB and NLRP3 inflammasome activation while promoting anti-inflammatory signaling via the JAK2/STAT3 and PI3K/Akt pathways. It also influences microglial polarization toward the reparative M2 phenotype and modulates BBB permeability and gut–brain axis interactions. Notably, EA has demonstrated synergistic potential when combined with pharmacologic agents such as l-DOPA, selegiline, donepezil, and minocycline, enhancing neuroprotective efficacy and reducing inflammatory and oxidative burdens. This highlights EA's potential integration into clinical strategies for treating neurodegenerative disorders. Understanding the neural circuits and immunological cascades engaged by EA may inform its future integration with pharmacotherapy in personalized neuroimmune interventions.

神经炎症在许多神经和神经退行性疾病的发病机制中起着核心作用，由神经胶质活化、细胞因子释放、血脑屏障（BBB）功能障碍和自主神经失调之间的复杂相互作用驱动。虽然针对炎症介质的药物治疗显示出希望，但其疗效往往受到血脑屏障通透性差和全身副作用的限制。电针（EA）是一种结合针灸和电刺激的神经调节技术，已成为一种很有前途的调节神经免疫动力学的辅助干预手段。EA激活定义的体感传入事件，并将信号传递到关键的自主神经和边缘核，包括脑干和下丘脑，这些核调节免疫反应。在分子水平上，EA抑制TLR4/NF- κB和NLRP3炎性小体激活等促炎通路，同时通过JAK2/STAT3和PI3K/Akt通路促进抗炎信号传导。它还影响小胶质细胞向修复性M2表型的极化，调节血脑屏障的通透性和肠-脑轴的相互作用。值得注意的是，EA与l-DOPA、selegiline、donepezil和米诺环素等药物联合使用时显示出协同作用潜力，增强神经保护功效，减少炎症和氧化负担。这突出了EA在治疗神经退行性疾病的临床策略中的潜在整合。了解EA参与的神经回路和免疫级联可以为其在个性化神经免疫干预中与药物治疗的未来整合提供信息。

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引用次数: 0

Pharmacoutilization data-driven artificial intelligence–assisted diagnosis algorithm to improve the pharmacological treatment of pain and agitation in patients suffering from severe dementia 药物利用数据驱动的人工智能辅助诊断算法改善重度痴呆患者疼痛和躁动的药物治疗

IF 4.2 3区医学 Q1 PHARMACOLOGY & PHARMACY

Current Opinion in Pharmacology

Pub Date : 2025-07-28 DOI: 10.1016/j.coph.2025.102563

Damiana Scuteri , Carlo Adornetto , Gianluigi Greco , Pierluigi Nicotera , Giacinto Bagetta , Maria Tiziana Corasaniti

The number of diagnoses and drug prescriptions for dementia patients is poorly available. Delay in the diagnosis of Alzheimer's disease (AD), for which missed diagnoses amount to over half cases, and undertreatment of chronic and neuropathic pain mirroring excessive use of harmful antipsychotics and antidepressants is reported. Our study aimed at diagnosing AD through the most advanced artificial intelligence (AI) methodologies even in patients who escaped clinical observation. To this end, pharmacoepidemiology data collected as part of the first retrospective community study in a wide sample of 298,000 individuals, 84,235 aged over 60 years, were used to set up an AI algorithm for the rescue of missed diagnoses of AD. The core of the algorithm consisted in the management of time series represented by pharmacological therapies through a distance matrix and in the use of autoencoders. Patients without a diagnosis of AD based on pharmacotherapy were 114.920, while diagnosed patients were 1.150, mainly aged between 75 and 84 years, pointing at late start of treatment. Increased use of antidepressants, neuroleptics, and mood stabilizers is found in patients treated with acetylcholinesterase inhibitors (AChEIs) and memantine, while nonsteroidal anti-inflammatory drugs, paracetamol–codeine and opioids are mostly prescribed to patients not receiving AChEIs and memantine. The classification model demonstrated good global accuracy at the end of training, equal to 79.12%. Further studies and longitudinal monitoring of patients are needed to improve disease detection and management. The deep learning–based pharmacoutilization algorithm generated in the present study will aid the diagnosis of AD and the understanding of neuropsychiatric symptoms treatment.

痴呆症患者的诊断和药物处方数量很少。据报道，阿尔茨海默病（AD）的诊断延误，漏诊率超过一半，慢性和神经性疼痛治疗不足，反映了有害抗精神病药物和抗抑郁药物的过度使用。我们的研究旨在通过最先进的人工智能（AI）方法诊断阿尔茨海默病，即使是在逃避临床观察的患者中。为此，作为首次回顾性社区研究的一部分收集的药物流行病学数据用于建立AI算法，以挽救AD的漏诊，该研究涵盖了298,000名年龄在60岁以上的个体，其中84,235人。该算法的核心是通过距离矩阵对以药物治疗为代表的时间序列进行管理，并使用自编码器。经药物治疗未确诊为AD的患者为114.920例，确诊患者为1.150例，主要年龄在75 ~ 84岁之间，说明治疗开始较晚。在接受乙酰胆碱酯酶抑制剂（AChEIs）和美金刚治疗的患者中，抗抑郁药、神经抑制剂和情绪稳定剂的使用增加，而非甾体类抗炎药、扑热息痛-可待因和阿片类药物大多用于未接受AChEIs和美金刚治疗的患者。在训练结束时，该分类模型具有良好的全局准确率，达到79.12%。需要进一步的研究和患者的纵向监测，以改善疾病的检测和管理。本研究生成的基于深度学习的药物利用算法将有助于AD的诊断和对神经精神症状治疗的理解。

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引用次数: 0

Corrigendum to “From “contraindicated” to “first line” – Current mechanistic insights beyond canonical β-receptor signaling” [COPHAR 76 (2024) 102458] “从“禁忌症”到“一线”-目前超越标准β受体信号传导的机制见解”的更正[COPHAR 76 (2024) 102458]

IF 4 3区医学 Q1 PHARMACOLOGY & PHARMACY

Current Opinion in Pharmacology

Pub Date : 2025-07-19 DOI: 10.1016/j.coph.2025.102550

Theresa Brand , Ann-Kathrin Lukannek , Valérie Jahns , Roland Jahns , Kristina Lorenz

引用次数: 0

Corrigendum to “Challenges in formulating transdermal systems for treating chronic skin infections” [Curr Opin Pharmacol 83 (2025) 102540] “制定治疗慢性皮肤感染的透皮系统所面临的挑战”的勘误表[现行药物管理83 (2025)102540]

IF 4 3区医学 Q1 PHARMACOLOGY & PHARMACY

Current Opinion in Pharmacology

Pub Date : 2025-07-16 DOI: 10.1016/j.coph.2025.102554

Akshay Ramchandra Yadav , Shital Aniket Shinde , Shubhangi B. Sutar , Snehal Aditya Arvindekar , Dwi Marlina Syukri

引用次数: 0

Recent innovations in clinical trial design for inflammatory bowel disease 炎症性肠病临床试验设计的最新创新

IF 4.2 3区医学 Q1 PHARMACOLOGY & PHARMACY

Current Opinion in Pharmacology

Pub Date : 2025-07-05 DOI: 10.1016/j.coph.2025.102551

Rocio Sedano , Christopher Ma , Vipul Jairath

Clinical trial design in inflammatory bowel disease (IBD) is evolving to address challenges in drug development and approvals. For clinical development, notable innovations include Bayesian designs, adaptive designs, integrated-phase trials and master protocols (such as umbrella, basket, and platform trials). The inclusion of biomarker-driven strategies and precision medicine (PM) trials bring aim to enable patient stratification based on prognostic or predictive markers, leveraging molecular signatures to customize therapy. However, recent studies highlight both the promise and complexity of this approach. Patient-reported outcomes (PROs) have gained prominence as key endpoints, aligning trials with patient-centric measures and regulatory guidance that emphasize symptoms and quality-of-life metrics. Digital health tools and artificial intelligence (AI) are being integrated to streamline trial conduct, from remote monitoring and telemedicine visits to AI-assisted recruitment and data analysis. Pragmatic trials and the integration of real-world evidence (RWE) aim to complement traditional efficacy trials by evaluating treatments in routine care settings. Together, these innovations mark a new era in IBD clinical trial design, aiming to expedite therapeutic development and enhance the relevance of trials to patient care.

炎症性肠病（IBD）的临床试验设计正在不断发展，以应对药物开发和批准方面的挑战。对于临床开发，值得注意的创新包括贝叶斯设计、自适应设计、综合阶段试验和主方案（如伞式、篮子式和平台试验）。包括生物标志物驱动的策略和精准医学（PM）试验，旨在实现基于预后或预测标记的患者分层，利用分子特征来定制治疗。然而，最近的研究强调了这种方法的前景和复杂性。患者报告的结果（pro）作为关键终点已获得突出地位，使试验与以患者为中心的措施和强调症状和生活质量指标的监管指南保持一致。正在整合数字卫生工具和人工智能（AI），以简化试验进行，从远程监测和远程医疗就诊到人工智能辅助招聘和数据分析。实用试验和现实世界证据整合（RWE）旨在通过评估常规护理环境中的治疗来补充传统疗效试验。总之，这些创新标志着IBD临床试验设计的新时代，旨在加快治疗开发并增强试验与患者护理的相关性。

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引用次数: 0

Smart solutions for tough infections: The rise of next-gen transdermal drug delivery 针对严重感染的智能解决方案：新一代经皮给药技术的兴起

IF 4 3区医学 Q1 PHARMACOLOGY & PHARMACY

Current Opinion in Pharmacology

Pub Date : 2025-07-03 DOI: 10.1016/j.coph.2025.102552

Sachin S. Mali, Prakash D. Jadhav, Sameer J. Nadaf

引用次数: 0

Molecular insights driving personalized therapies 分子洞察推动个性化治疗

IF 4 3区医学 Q1 PHARMACOLOGY & PHARMACY

Current Opinion in Pharmacology

Pub Date : 2025-07-02 DOI: 10.1016/j.coph.2025.102553

Kristina Lorenz, Jürgen Schrader

引用次数: 0

Ionic liquid choline and geranic acid-mediated topical drug delivery in skin tissue regeneration and neutralization of potential pathogens: A review 离子液体胆碱和天竺葵酸介导的局部药物递送在皮肤组织再生和潜在病原体中和中的研究进展

IF 4 3区医学 Q1 PHARMACOLOGY & PHARMACY

Current Opinion in Pharmacology

Pub Date : 2025-06-25 DOI: 10.1016/j.coph.2025.102549

Popat Mohite , Shubham Munde , Aarati Budar , Sudarshan Singh , Chuda Chittasupho

Ionic liquids have emerged as promising vehicles for drug delivery, with choline and geranic acid (CAGE) demonstrating exceptional potential in topical formulation for skin tissue regeneration and antimicrobial properties. CAGE exhibits unique physicochemical properties such as viscosity, high ionic conductivity, and enhanced solubility that contribute to efficacy in enhanced drug permeation with controlled drug release. CAGE possesses the inherent antimicrobial properties, making it an ideal candidate for the management of dermal complications. The review discusses the recent advancements in CAGE-oriented formulations, emphasizing their role in wound healing, followed by formulation strategies and key process parameters.

离子液体已经成为药物输送的有前途的载体，胆碱和天竺葵酸（CAGE）在皮肤组织再生和抗菌特性的局部配方中显示出非凡的潜力。CAGE具有独特的物理化学性质，如粘度、高离子电导率和增强的溶解度，有助于增强药物渗透和控制药物释放。CAGE具有固有的抗菌特性，使其成为管理皮肤并发症的理想人选。本文综述了近年来以cage为导向的配方的进展，强调了它们在伤口愈合中的作用，其次是配方策略和关键工艺参数。

引用次数: 0

Nanotechnology-enhanced transdermal systems for infectious diseases 纳米技术增强的传染病透皮系统

IF 4 3区医学 Q1 PHARMACOLOGY & PHARMACY

Current Opinion in Pharmacology

Pub Date : 2025-06-20 DOI: 10.1016/j.coph.2025.102547

Swati Udugade , Babaso V. Udugade , Sanket R. Patil , Ashwini C. Utage , Shagun Swaroop

Nanotechnology-enhanced transdermal drug delivery systems (NETS) show great potential in treating infectious diseases by improving drug penetration, stability, and bioavailability. Unlike traditional methods, NETS overcome skin barrier limitations through the use of lipid-based, polymeric nanoparticles, and dendrimers, enabling efficient drug transport and controlled release. This results in enhanced therapeutic efficacy and reduced systemic side effects for bacterial, viral, and fungal infections. However, challenges related to toxicity, stability, and regulatory hurdles remain. This paper examines the mechanisms, advantages, and limitations of NETS, while highlighting promising future research opportunities and clinical applications in combating infectious diseases.

纳米技术增强的经皮给药系统（NETS）通过改善药物渗透、稳定性和生物利用度，在治疗传染病方面显示出巨大的潜力。与传统方法不同，NETS通过使用基于脂质、聚合纳米颗粒和树突状大分子，克服了皮肤屏障的限制，实现了有效的药物运输和控制释放。这提高了治疗效果，减少了对细菌、病毒和真菌感染的全身副作用。然而，与毒性、稳定性和监管障碍相关的挑战仍然存在。本文探讨了网络的机制、优势和局限性，同时强调了未来在防治传染病方面的研究机会和临床应用。

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全部化学•材料生命科学医学物理工程技术环境•农林材料科学地球科学法学管理学化学环境科学与生态学计算机科学教育学经济学农林科学人文科学生物学数学物理与天体物理心理学综合性期刊其他工业工程理学历史学农学文学信息工程

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