Pharmacology & Therapeutics最新文献

{"title":"Oxytocin in neurodevelopmental disorders: Autism spectrum disorder and Prader-Willi syndrome","authors":"Alyssa Josselsohn ,&nbsp;Yin Zhao ,&nbsp;Danielle Espinoza ,&nbsp;Eric Hollander","doi":"10.1016/j.pharmthera.2024.108734","DOIUrl":"10.1016/j.pharmthera.2024.108734","url":null,"abstract":"<div><div>This manuscript reviews recent work on oxytocin and its use in neurodevelopmental disorders including spectrum disorder (ASD) and Prader-Willi syndrome (PWS). Oxytocin is involved in social recognition, bonding, maternal behaviors, anxiety, food motivation, and hyperphagia. While the pathophysiology of ASD and PWS involve abnormalities in the oxytocin system, clinical trials have shown discrepant results in the effectiveness of oxytocin as a treatment for core symptoms associated with these disorders. In this review, we outline oxytocin's clinical pharmacology, safety considerations, and results in recent clinical trials. We propose that oxytocin may be most beneficial in these populations if dosed in a dynamic regimen (PRN) and paired with social interventions.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"264 ","pages":"Article 108734"},"PeriodicalIF":12.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural products that alleviate depression: The putative role of autophagy","authors":"Yunfeng Zhou ,&nbsp;Fengwei Nan ,&nbsp;Qianwen Zhang ,&nbsp;Wangjun Xu ,&nbsp;Shaojie Fang ,&nbsp;Ke Liu ,&nbsp;Bingxin Zhao ,&nbsp;Hao Han ,&nbsp;Xinmei Xie ,&nbsp;Changjiang Qin ,&nbsp;Xiaobin Pang","doi":"10.1016/j.pharmthera.2024.108731","DOIUrl":"10.1016/j.pharmthera.2024.108731","url":null,"abstract":"<div><div>Major depressive disorder (MDD) is a common mental disorder that severely disrupts psychosocial function and decreases the quality of life. Although the pathophysiological mechanism underlying MDD is complex and remains unclear, emerging evidence suggests that autophagy dysfunction plays a role in MDD occurrence and progression. Natural products serve as a major source of drug discovery and exert tremendous potential in developing antidepressants. Recently published reports are paying more attention on the autophagy regulatory effect of antidepressant natural products. In this review, we comprehensively discuss the abnormal changes occurred in multiple autophagy stages in MDD patients, and animal and cell models of depression. Importantly, we emphasize the regulatory mechanism of antidepressant natural products on disturbed autophagy, including monomeric compounds, bioactive components, crude extracts, and traditional Chinese medicine formulae. Our comprehensive review suggests that enhancing autophagy might be a novel approach for MDD treatment, and natural products restore autophagy homeostasis to facilitate the renovation of mitochondria, impede neuroinflammation, and enhance neuroplasticity, thereby alleviating depression.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"264 ","pages":"Article 108731"},"PeriodicalIF":12.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comprehensive review on pharmacokinetic mechanism of herb-herb/drug interactions in Chinese herbal formula","authors":"Mengting Li ,&nbsp;Yanli Wang ,&nbsp;Yi Chen ,&nbsp;Lijinchuan Dong ,&nbsp;Jieyuan Liu ,&nbsp;Yu Dong ,&nbsp;Qing Yang ,&nbsp;Weiyan Cai ,&nbsp;Qi Li ,&nbsp;Bo Peng ,&nbsp;Yujie Li ,&nbsp;Xiaogang Weng ,&nbsp;Yajie Wang ,&nbsp;Xiaoxin Zhu ,&nbsp;Zipeng Gong ,&nbsp;Ying Chen","doi":"10.1016/j.pharmthera.2024.108728","DOIUrl":"10.1016/j.pharmthera.2024.108728","url":null,"abstract":"<div><div>Oral administration of Chinese Herbal Medicine (CHM) faces various challenges in reaching the target organs including absorption and conversion in the gastrointestinal tract, hepatic metabolism <em>via</em> the portal vein, and eventual systemic circulation. During this process, factors such as gut microbes, physical or chemical barriers, metabolic enzymes, and transporters play crucial roles. Particularly, interactions between different herbs in CHM have been observed both <em>in vitro</em> and <em>in vivo</em>. <em>In vitro</em>, interactions typically manifest as detectable physical or chemical changes, such as facilitating solubilization or producing precipitates when decoctions of multiple herbs are administered. <em>In vivo</em>, such interactions cause alterations in the ADME (absorption, distribution, metabolism, and excretion) profile on metabolic enzymes or transporters in the body, leading to competition, antagonism, inhibition, or activation. These interactions ultimately contribute to differences in the therapeutic and pharmacological effects of multi-herb formulas in CHM. Over the past two thousand years, China has cultivated profound expertise and solid theoretical frameworks over the scientific use of herbs. The combination of multiple herbs in one decoction has been frequently employed to synergistically enhance therapeutic efficacy or mitigate toxic and side effects in clinical settings. Additionally combining herbs with increased toxicity or decreased effect is also regarded as a remedy, a practice that should be approached with caution according to Traditional Chinese Medicine (TCM) physicians. Such historical records and practices serve as a foundation for predicting favorable multi-herb combinations and their potential risks. However, systematic data that are available to support the clinical practice and the exploration of novel herbal formulas remain limited. Therefore, this review aims to summarize the pharmacokinetic interactions and mechanisms of herb-herb or herb-drug combinations from existing works, and to offer guidance as well as evidence for optimizing CHM and developing new medicines with CHM characteristics.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"264 ","pages":"Article 108728"},"PeriodicalIF":12.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142398997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulating glucocorticoid receptor actions in physiology and pathology: Insights from coregulators","authors":"Lina Fadel ,&nbsp;Marija Dacic ,&nbsp;Vlera Fonda ,&nbsp;Baila A. Sokolsky ,&nbsp;Fabiana Quagliarini ,&nbsp;Inez Rogatsky ,&nbsp;N. Henriette Uhlenhaut","doi":"10.1016/j.pharmthera.2023.108531","DOIUrl":"10.1016/j.pharmthera.2023.108531","url":null,"abstract":"<div><p>Glucocorticoids (GCs) are a class of steroid hormones that regulate key physiological processes such as metabolism, immune function, and stress responses. The effects of GCs are mediated by the glucocorticoid receptor (GR), a ligand-dependent transcription factor that activates or represses the expression of hundreds to thousands of genes in a tissue- and physiological state-specific manner. The activity of GR is modulated by numerous coregulator proteins that interact with GR in response to different stimuli assembling into a multitude of DNA-protein complexes and facilitate the integration of these signals, helping GR to communicate with basal transcriptional machinery and chromatin. Here, we provide a brief overview of the physiological and molecular functions of GR, and discuss the roles of GR coregulators in the immune system, key metabolic tissues and the central nervous system. We also present an analysis of the GR interactome in different cells and tissues, which suggests tissue-specific utilization of GR coregulators, despite widespread functions shared by some of them.</p></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"251 ","pages":"Article 108531"},"PeriodicalIF":13.5,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S016372582300195X/pdfft?md5=35115605c8fbdbcd6f444bf2476b765d&pid=1-s2.0-S016372582300195X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10286424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Towards precision medicine in migraine: Recent therapeutic advances and potential biomarkers to understand heterogeneity and treatment response","authors":"Gabriella Juhasz ,&nbsp;Kinga Gecse ,&nbsp;Daniel Baksa","doi":"10.1016/j.pharmthera.2023.108523","DOIUrl":"10.1016/j.pharmthera.2023.108523","url":null,"abstract":"<div><p>After 35 years since the introduction of the International Classification of Headache Disorders (ICHD), we are living in the era of the second great revolution in migraine therapies. First, discoveries of triptans provided a breakthrough in acute migraine treatment utilizing bench-to-bedside research results on the role of serotonin in migraine. Next, the discovery of the role of neuropeptides, more specifically calcitonin gene-related peptide (CGRP) in migraine attack led to the development of anti-CGRP therapies that are effective both in acute and preventive treatment, and are also able to reduce migraine-related burden. Here, we reviewed the most recent clinical studies and real-world data on available migraine-specific medications, including triptans, ditants, gepants and anti-CGRP monoclonal antibodies. Novel drug targets, such as PACAP and amylins were also discussed. To address the main challenges of migraine therapy, the high heterogeneity of people with migraine, the prevalent presence of various comorbid disorders, and the insufficient medical care of migraine patients were covered. Promising novel approaches from the fields of omics, blood and saliva biomarker, imaging and provocation studies might bring solutions for these challenges with the potential to identify further drug targets, distinguish more homogeneous patient subgroups, contribute to more optimal drug selection strategies, and detect biomarkers in association with headache features or predicting treatment efficacy. In the future, the combined analysis of data of different biomarker modalities with machine learning algorithms may serve precision medicine in migraine treatment.</p></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"250 ","pages":"Article 108523"},"PeriodicalIF":13.5,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0163725823001870/pdfft?md5=81680097c990d9d79d3b5b995e293505&pid=1-s2.0-S0163725823001870-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10262940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond statins: New pharmacological targets to decrease LDL-cholesterol and cardiovascular events","authors":"Emanuel Raschi ,&nbsp;Manuela Casula ,&nbsp;Arrigo F.G. Cicero ,&nbsp;Alberto Corsini ,&nbsp;Claudio Borghi ,&nbsp;Alberico Catapano","doi":"10.1016/j.pharmthera.2023.108507","DOIUrl":"10.1016/j.pharmthera.2023.108507","url":null,"abstract":"<div><p>The pharmacological treatment of dyslipidemia, a major modifiable risk factor for developing atherosclerotic cardiovascular disease (ASCVD), remains a debated and controversial issue, not only in terms of the most appropriate therapeutic range for lipid levels, but also with regard to the optimal strategy and sequence approach (stepwise vs upstream therapy). Current treatment guidelines for the management of dyslipidemia focus on the intensity of low-density lipoprotein cholesterol (LDL-C) reduction, stratified according to risk for developing ASCVD. Beyond statins and ezetimibe, different medications targeting LDL-C have been recently approved by regulatory agencies with potential innovative mechanisms of action, including proprotein convertase subtilisin/kexin type 9 modulators (monoclonal antibodies such as evolocumab and alirocumab; small interfering RNA molecules such as inclisiran), ATP-citrate lyase inhibitors (bempedoic acid), angiopoietin-like 3 inhibitors (evinacumab), and microsomal triglyceride transfer protein inhibitors (lomitapide). An understanding of their pharmacological aspects, benefit-risk profile, including impact on hard cardiovascular endpoints beyond LDL-C reduction, and potential advantages from the patient perspective (e.g., adherence) - the focus of this evidence-based review - is crucial for practitioners across medical specialties to minimize therapeutic inertia and support clinical practice.</p></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"250 ","pages":"Article 108507"},"PeriodicalIF":13.5,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0163725823001717/pdfft?md5=be26cf6e3a8292a2d4218594983180fe&pid=1-s2.0-S0163725823001717-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10072383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antithrombotic therapy following transcatheter aortic valve intervention","authors":"Harish Sharma ,&nbsp;Shazia Afzal ,&nbsp;Jürgen Leick ,&nbsp;Nikos Werner ,&nbsp;Sagar N. Doshi ,&nbsp;M. Adnan Nadir","doi":"10.1016/j.pharmthera.2023.108509","DOIUrl":"10.1016/j.pharmthera.2023.108509","url":null,"abstract":"<div><p><span>Transcatheter aortic valve replacement (TAVR) is increasingly being performed to treat symptomatic patients with aortic stenosis and annual procedure volume has overtaken surgical aortic valve replacement in the United States. However, current international guidelines were written prior to the publication of several important recent studies. Furthermore, European and American guidelines differ in their recommendations of </span>antithrombotic therapy<span> following TAVR. Consequently, there is a need to examine the literature to provide clinicians guidance on the optimum antithrombotic strategy, particularly as different patient populations exist. In this review, we examine the data for antiplatelet and anticoagulation therapy post-TAVR.</span></p></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"250 ","pages":"Article 108509"},"PeriodicalIF":13.5,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10192088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposing of antiangiogenic agents for treatment of vascular anomalies","authors":"Julie Blatt ,&nbsp;Jennifer E. Brondon ,&nbsp;Elizabeth L. Nieman ,&nbsp;Kynlon Phillips ,&nbsp;Arti Pandya","doi":"10.1016/j.pharmthera.2023.108520","DOIUrl":"10.1016/j.pharmthera.2023.108520","url":null,"abstract":"<div><p><span>Vascular anomalies<span> (VA) are developmental anomalies of veins, arteries, lymphatics or capillaries thought to be caused by mutations in genes that drive angiogenesis. Treatments targeting these genes are limited. We review the literature for conventional medications and products from traditional medicine cultures that have been found to have antiangiogenic<span> activity. Fewer than 50 drugs with credible human activity in VA were identified and include β blockers<span><span>, monoclonal antibodies, </span>microtubule inhibitors, multi-kinase inhibitors, </span></span></span></span><em>PIK3CA</em>- and <em>RAS-MAPK</em><span> pathway inhibitors, and thalidomides. Other drug categories of potential interest are ACE-inhibitors, antifungals<span>, antimalarials, </span></span><span><em>MMP9</em></span><span>-inhibitors, and over-the-counter compounds used in Eastern traditional medicine. Low toxicity for some offers the possibility of combined use with known effective agents. In addition to already familiar drugs, others with antiangiogenic capabilities already in use in children or adults may deserve further attention for repurposing for VA.</span></p></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"250 ","pages":"Article 108520"},"PeriodicalIF":13.5,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10539692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer metastasis: Molecular mechanisms and clinical perspectives","authors":"Sameer Ullah Khan ,&nbsp;Kaneez Fatima ,&nbsp;Fayaz Malik ,&nbsp;Halime Kalkavan ,&nbsp;Abubakar Wani","doi":"10.1016/j.pharmthera.2023.108522","DOIUrl":"10.1016/j.pharmthera.2023.108522","url":null,"abstract":"<div><p>Metastatic progression combined with non-responsiveness towards systemic therapy often shapes the course of disease for cancer patients and commonly determines its lethal outcome. The complex molecular events that promote metastasis are a combination of both, the acquired pro-metastatic properties of cancer cells and a metastasis-permissive or -supportive tumor micro-environment (TME). Yet, dissemination is a challenging process for cancer cells that requires a series of events to enable cancer cell survival and growth. Metastatic cancer cells have to initially detach themselves from primary tumors, overcome the challenges of their intravasal journey and colonize distant sites that are suited for their metastases. The implicated obstacles including anoikis and immune surveillance, can be overcome by intricate intra- and extracellular signaling pathways, which we will summarize and discuss in this review. Further, emerging modulators of metastasis, like the immune-microenvironment, microbiome, sublethal cell death engagement, or the nervous system will be integrated into the existing working model of metastasis.</p></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"250 ","pages":"Article 108522"},"PeriodicalIF":13.5,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10194523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticancer drug delivery by focused ultrasound-mediated blood-brain/tumor barrier disruption for glioma therapy: From benchside to bedside","authors":"Charlotte Bérard ,&nbsp;Charles Truillet ,&nbsp;Benoit Larrat ,&nbsp;Frédéric Dhermain ,&nbsp;Marie-Anne Estève ,&nbsp;Florian Correard ,&nbsp;Anthony Novell","doi":"10.1016/j.pharmthera.2023.108518","DOIUrl":"10.1016/j.pharmthera.2023.108518","url":null,"abstract":"<div><p><span>The therapeutic management of gliomas remains particularly challenging. Brain tumors present multiple obstacles that make therapeutic innovation complex, mainly due to the presence of blood-tumor and blood-brain barriers (BTB and BBB, respectively) which prevent penetration of anticancer agents into the brain parenchyma. Focused ultrasound-mediated BBB disruption (FUS-BBBD) provides a physical method for non-invasive, local, and reversible BBB disruption. The safety of this technique has been demonstrated in small and large animal models. This approach promises to enhance drug delivery into the brain tumor and therefore to improve survival outcomes by </span>repurposing<span><span> existing drugs. Several clinical trials continue to be initiated in the last decade. In this review, we provide an overview of the rationale behind the use of FUS-BBBD in gliomas and summarize the </span>preclinical studies investigating different approaches (free drugs, drug-loaded microbubbles and drug-loaded nanocarriers) in combination with this technology in in vivo glioma models. Furthermore, we discuss the current state of clinical trials and devices developed and review the challenges to overcome for clinical use of FUS-BBBD in glioma therapy.</span></p></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"250 ","pages":"Article 108518"},"PeriodicalIF":13.5,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10129849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}