Drugs最新文献

{"title":"Vunakizumab: First Approval.","authors":"Susan J Keam","doi":"10.1007/s40265-024-02110-8","DOIUrl":"https://doi.org/10.1007/s40265-024-02110-8","url":null,"abstract":"<p><p>Vunakizumab (^®) is a subcutaneous (SC) recombinant anti-interleukin (IL)-17A humanized monoclonal IgG1/κ antibody being developed by Suzhou Suncadia Biopharmaceutical Co., Ltd (a subsidiary of Jiangsu Hengrui Pharmaceuticals Co., Ltd) for the systemic treatment of autoimmune diseases related to the IL-17 pathway, including psoriasis, ankylosing spondylitis and psoriatic arthritis. In August 2024, vunakizumab was approved in China for the treatment of adult patients with moderate-to-severe plaque psoriasis who are suitable for systemic treatment or phototherapy. This article summarizes the milestones in the development of vunakizumab leading to this first approval for the systemic treatment of moderate-to-severe plaque psoriasis.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575627","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":"Update on Mpox Management: Epidemiology, Vaccines and Therapeutics, and Regulatory Changes.","authors":"Youssef Rizk, Giuseppe Lippi, Brandon M Henry, Kin Israel Notarte, John G Rizk","doi":"10.1007/s40265-024-02117-1","DOIUrl":"https://doi.org/10.1007/s40265-024-02117-1","url":null,"abstract":"<p><p>Mpox, caused by the monkeypox virus (MPXV), is categorized into two primary clades: Clade I and Clade II, with notable outbreaks linked to Clade IIb. Historically endemic in Africa, recent years have seen significant global spread. The World Health Organization (WHO) declared mpox a Public Health Emergency of International Concern in August 2024, highlighting the emergence of Clade Ib outside Africa and the broadening demographic impact of the outbreak. This review updates the current status of mpox vaccines and treatments, including their safety and effectiveness. There are two US Food and Drug Administration (FDA)-approved vaccines for the prevention of mpox disease, Jynneos^TM and ACAM2000^®. The Jynneos^TM vaccine, recommended for high-risk individuals, has seen limited uptake despite its efficacy in preventing disease. Tecovirimat, while FDA-approved for smallpox and available in the European Union for mpox, has shown mixed results in recent trials, with new data suggesting limited effectiveness in Clade I infections and emergence of new mutations with resistance to this drug. Brincidofovir and Vaccinia Immune Globulin Intravenous offer additional treatment options, particularly for severe cases, although their use is constrained by regulatory and logistical challenges. Furthermore, the WHO recently approved the first commercial molecular assay, the Alinity m MPXV assay by Abbott Molecular Inc., for emergency use-an essential step in expanding testing capacity in regions experiencing mpox outbreaks. These updates underscore the critical need for continued research to enhance therapeutic outcomes and adapt public health strategies. Ensuring equitable access to vaccines, treatments, and diagnostics remains a significant challenge as the global community responds to the evolving mpox situation.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575624","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":"2024 Recommendations on the Optimal Use of Lipid-Lowering Therapy in Established Atherosclerotic Cardiovascular Disease and Following Acute Coronary Syndromes: A Position Paper of the International Lipid Expert Panel (ILEP).","authors":"Maciej Banach, Željko Reiner, Stanisław Surma, Gani Bajraktari, Agata Bielecka-Dabrowa, Matjaz Bunc, Ibadete Bytyçi, Richard Ceska, Arrigo F G Cicero, Dariusz Dudek, Krzysztof Dyrbuś, Jan Fedacko, Zlatko Fras, Dan Gaita, Dov Gavish, Marek Gierlotka, Robert Gil, Ioanna Gouni-Berthold, Piotr Jankowski, Zoltán Járai, Jacek Jóźwiak, Niki Katsiki, Gustavs Latkovskis, Stefania Lucia Magda, Eduard Margetic, Roman Margoczy, Olena Mitchenko, Azra Durak-Nalbantic, Petr Ostadal, Gyorgy Paragh, Zaneta Petrulioniene, Francesco Paneni, Ivan Pećin, Daniel Pella, Arman Postadzhiyan, Anca Pantea Stoian, Matias Trbusic, Cristian Alexandru Udroiu, Margus Viigimaa, Dragos Vinereanu, Charalambos Vlachopoulos, Michal Vrablik, Dusko Vulic, Peter E Penson","doi":"10.1007/s40265-024-02105-5","DOIUrl":"https://doi.org/10.1007/s40265-024-02105-5","url":null,"abstract":"<p><p>Atherosclerotic cardiovascular disease (ASCVD) and consequent acute coronary syndromes (ACS) are substantial contributors to morbidity and mortality across Europe. Fortunately, as much as two thirds of this disease's burden is modifiable, in particular by lipid-lowering therapy (LLT). Current guidelines are based on the sound premise that, with respect to low-density lipoprotein cholesterol (LDL-C), \"lower is better for longer\", and recent data have strongly emphasised the need for also \"the earlier the better\". In addition to statins, which have been available for several decades, ezetimibe, bempedoic acid (also as fixed dose combinations), and modulators of proprotein convertase subtilisin/kexin type 9 (PCSK9 inhibitors and inclisiran) are additionally very effective approaches to LLT, especially for those at very high and extremely high cardiovascular risk. In real life, however, clinical practice goals are still not met in a substantial proportion of patients (even in 70%). However, with the options we have available, we should render lipid disorders a rare disease. In April 2021, the International Lipid Expert Panel (ILEP) published its first position paper on the optimal use of LLT in post-ACS patients, which complemented the existing guidelines on the management of lipids in patients following ACS, which defined a group of \"extremely high-risk\" individuals and outlined scenarios where upfront combination therapy should be considered to improve access and adherence to LLT and, consequently, the therapy's effectiveness. These updated recommendations build on the previous work, considering developments in the evidential underpinning of combination LLT, ongoing education on the role of lipid disorder therapy, and changes in the availability of lipid-lowering drugs. Our aim is to provide a guide to address this unmet clinical need, to provide clear practical advice, whilst acknowledging the need for patient-centred care, and accounting for often large differences in the availability of LLTs between countries.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575616","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":"The Challenge of Treating Infections Caused by Metallo-β-Lactamase-Producing Gram-Negative Bacteria: A Narrative Review.","authors":"Carmen Hidalgo-Tenorio, German Bou, Antonio Oliver, Montserrat Rodríguez-Aguirregabiria, Miguel Salavert, Luis Martínez-Martínez","doi":"10.1007/s40265-024-02102-8","DOIUrl":"https://doi.org/10.1007/s40265-024-02102-8","url":null,"abstract":"<p><p>Gram-negative multidrug-resistant (MDR) bacteria, including Enterobacterales, Acinetobacter baumannii, and Pseudomonas aeruginosa, pose a significant challenge in clinical practice. Infections caused by metallo-β-lactamase (MBL)-producing Gram-negative organisms, in particular, require careful consideration due to their complexity and varied prevalence, given that the microbiological diagnosis of these pathogens is intricate and compounded by challenges in assessing the efficacy of anti-MBL antimicrobials. We discuss both established and new approaches in the treatment of MBL-producing Gram-negative infections, focusing on 3 strategies: colistin; the recently approved combination of aztreonam with avibactam (or with ceftazidime/avibactam); and cefiderocol. Despite its significant activity against various Gram-negative pathogens, the efficacy of colistin is limited by resistance mechanisms, while nephrotoxicity and acute renal injury call for careful dosing and monitoring in clinical practice. Aztreonam combined with avibactam (or with avibactam/ceftazidime if aztreonam plus avibactam is not available) exhibits potent activity against MBL-producing Gram-negative pathogens. Cefiderocol in monotherapy is effective against a wide range of multidrug-resistant organisms, including MBL producers, and favorable clinical outcomes have been observed in various clinical trials and case series. After examining scientific evidence in the management of infections caused by MBL-producing Gram-negative bacteria, we have developed a comprehensive clinical algorithm to guide therapeutic decision making. We recommend reserving colistin as a last-resort option for MDR Gram-negative infections. Cefiderocol and aztreonam/avibactam represent favorable options against MBL-producing pathogens. In the case of P. aeruginosa with MBL-producing enzymes and with difficult-to-treat resistance, cefiderocol is the preferred option. Further research is needed to optimize treatment strategies and minimize resistance.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521365","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 Meta-analysis Exploring the Efficacy of Neuropathic Pain Medication for Low Back Pain or Spine-Related Leg Pain: Is Efficacy Dependent on the Presence of Neuropathic Pain?","authors":"Jennifer Ward, Anthony Grinstead, Amy Kemp, Paula Kersten, Annina B Schmid, Colette Ridehalgh","doi":"10.1007/s40265-024-02085-6","DOIUrl":"10.1007/s40265-024-02085-6","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objective: &lt;/strong&gt;Highly variable pain mechanisms in people with low back pain or spine-related leg pain might contribute to inefficacy of neuropathic pain medication. This meta-analysis aimed to determine how neuropathic pain is identified in clinical trials for people taking neuropathic pain medication for low back pain or spine-related leg pain and whether subgrouping based on the presence of neuropathic pain influences efficacy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;EMBASE, MEDLINE, Cochrane Central, CINAHL [EBSCO], APA PsycINFO, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry were searched from inception to 14 May, 2024. Randomized and crossover trials comparing first-line neuropathic pain medication for people with low back pain or spine-related leg pain to placebo or usual care were included. Two independent authors extracted data. Random-effects meta-analyses of all studies combined, and pre-planned subgroup meta-analyses based on the certainty of neuropathic pain (according to the neuropathic pain Special Interest Group [NeuPSIG] neuropathic pain grading criteria) were completed. Certainty of evidence was judged using the grading of recommendations assessment development and evaluation [GRADE] framework.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Twenty-seven included studies reported on 3619 participants. Overall, 33% of studies were judged unlikely to include people with neuropathic pain, 26% remained unclear. Only 41% identified people with possible, probable, or definite neuropathic pain. For pain, general analyses revealed only small effects at short term (mean difference [MD] - 9.30 [95% confidence interval [CI] - 13.71, - 4.88], I&lt;sup&gt;2&lt;/sup&gt; = 87%) and medium term (MD - 5.49 [95% CI - 7.24, - 3.74], I&lt;sup&gt;2&lt;/sup&gt; = 0%). Subgrouping at short term revealed studies including people with definite or probable neuropathic pain showed larger effects on pain (definite; MD - 16.65 [95% CI - 35.95, 2.65], I&lt;sup&gt;2&lt;/sup&gt; = 84%; probable; MD - 10.45 [95% CI - 14.79, - 6.12], I&lt;sup&gt;2&lt;/sup&gt; = 20%) than studies including people with possible (MD - 5.50 [95% CI - 20.52, 9.52], I&lt;sup&gt;2&lt;/sup&gt; = 78%), unlikely (MD - 6.67 [95% CI - 10.58, 2.76], I&lt;sup&gt;2&lt;/sup&gt; = 0%), or unclear neuropathic pain (MD - 8.93 [95% CI - 20.57, 2.71], I&lt;sup&gt;2&lt;/sup&gt; = 96%). Similarly, general analyses revealed negligible effects on disability at short term (MD - 3.35 [95% CI - 9.00, 2.29], I&lt;sup&gt;2&lt;/sup&gt; = 93%) and medium term (MD - 4.06 [95% CI - 5.63, - 2.48], I&lt;sup&gt;2&lt;/sup&gt; = 0%). Sub-grouping at short term revealed larger effects in studies including people with definite/probable neuropathic pain (MD - 9.25 [95% CI - 12.59, - 5.90], I&lt;sup&gt;2&lt;/sup&gt; = 2%) compared with those with possible/unclear/unlikely neuropathic pain (MD -1.57 [95% CI - 8.96, 5.82] I&lt;sup&gt;2&lt;/sup&gt; = 95%). Medium-term outcomes showed a similar trend, but were limited by low numbers of studies. Certainty of evidence was low to very low for all outcomes.","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7616789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497072","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":"How Psychedelics Modulate Multiple Memory Mechanisms in Posttraumatic Stress Disorder.","authors":"Manoj K Doss, AnnaMarie DeMarco, Joseph E Dunsmoor, Josh M Cisler, Gregory A Fonzo, Charles B Nemeroff","doi":"10.1007/s40265-024-02106-4","DOIUrl":"10.1007/s40265-024-02106-4","url":null,"abstract":"<p><p>Posttraumatic stress disorder (PTSD) is a psychiatric disorder with defining abnormalities in memory, and psychedelics may be promising candidates for the treatment of PTSD given their effects on multiple memory systems. Most PTSD and psychedelic research has investigated memory with fear conditioning and extinction. While fruitful, conditioning and extinction provide a limited model of the complexity of PTSD and phenomenology of psychedelics, thereby limiting the refinement of therapies. In this review, we discuss abnormalities in fear conditioning and extinction in PTSD and review 25 studies testing psychedelics on these forms of memory. Perhaps the most reliable effect is that the acute effects of psychedelics can enhance extinction learning, which is impaired in PTSD. However, the post-acute effects may also enhance extinction learning, and the acute effects can also enhance fear conditioning. We then discuss abnormalities in episodic and semantic memory in PTSD and review current knowledge on how psychedelics impact these memory systems. Although PTSD and psychedelics acutely impair the formation of hippocampal-dependent episodic memories, psychedelics may acutely enhance cortical-dependent learning of semantic memories that could facilitate the integration of trauma memories and disrupt maladaptive beliefs. More research is needed on the acute effects of psychedelics on episodic memory consolidation, retrieval, and reconsolidation and post-acute effects of psychedelics on all phases of episodic memory. We conclude by discussing how targeting multiple memory mechanisms could improve upon the current psychedelic therapy paradigm for PTSD, thereby necessitating a greater emphasis on assessing diverse measures of memory in translational PTSD and psychedelic research.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497073","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":"Trientine Tetrahydrochloride, From Bench to Bedside: A Narrative Review.","authors":"C Omar F Kamlin, Timothy M Jenkins, Jamie L Heise, Naseem S Amin","doi":"10.1007/s40265-024-02099-0","DOIUrl":"https://doi.org/10.1007/s40265-024-02099-0","url":null,"abstract":"<p><p>Trientine tetrahydrochloride (TETA-4HCl, Cuvrior^®) is a copper chelating agent with the active moiety triethylenetetramine (trientine), developed by Orphalan, Inc. to address the unmet needs in the treatment of Wilson disease. The journey from bench to bedside builds upon the documented safety profile of trientine hydrochloride capsules developed initially to meet the needs of individuals intolerant to D-penicillamine (DPA). Trientine hydrochloride capsules are inherently unstable requiring strict cold chain storage conditions from production, transportation, and use at home by the patient. Trientine tetrahydrochloride has a distinctive, patent-protected unique polymorphic form, which permits the production at scale of film-coated scored tablets deemed room temperature stable for 36 months. Trientine tetrahydrochloride is supported by a well-characterized pharmacodynamic, pharmacokinetic, and metabolic profile demonstrating reliable and predictable dose linearity and dose proportionality kinetics. Trientine tetrahydrochloride is the only trientine formulation that has been compared with DPA in a prospective randomized clinical trial, demonstrating non-inferiority to DPA in adults with stable Wilson disease. On 28 April, 2022, the US Food and Drug Administration approved TETA-4HCl for use in adult patients with Wilson disease who are de-coppered and tolerant to DPA. Health authorities in multiple countries worldwide have approved TETA-4HCl for the treatment of adults and children aged 5 years or more who are intolerant to DPA including the European Union, UK, Saudi Arabia, Switzerland, Colombia, Australia, New Zealand, and China. This article aims to provide a comprehensive narrative review of the key milestones in the development of TETA-4HCl.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460701","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":"Exploring Novel Pharmacotherapy Candidates for Cannabis Use Disorder: Uncovering Promising Agents on the Horizon by Mechanism of Action.","authors":"Myra Alayoubi, Brittany A Henry, Catherine M Cahill, Ziva D Cooper","doi":"10.1007/s40265-024-02098-1","DOIUrl":"https://doi.org/10.1007/s40265-024-02098-1","url":null,"abstract":"<p><p>With rapid expansion of cannabis legalization worldwide, rates of cannabis use and cannabis use disorder (CUD) are increasing; the need for safe and effective medications to treat CUD is urgent. This narrative review evaluates evidence for promising pharmacotherapies to treat CUD from randomized, placebo-controlled trials. Pharmacotherapies for CUD are categorized based on compound targets (e.g., cannabinoid receptor 1 [CB1] agonists such as nabilone, serotonergic compounds such as bupropion, GABAergic compounds such as zolpidem) and outcomes are organized by predetermined withdrawal symptoms, cannabis craving, and cannabis relapse/use. Most promising pharmacotherapies for CUD are drugs that act on the endocannabinoid system and specifically at the CB1 receptor. Priority populations such as females, certain racial/ethnic groups, and age groups experience a different course of CUD progression, symptoms, and drug effects that are important to consider when evaluating outcomes related to CUD. Possible explanations for these disparities are explored, along with the clinical trials that explore these demographics in treating CUD with pharmacotherapies.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460700","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":"Difficult-to-Treat Axial Spondyloarthritis: A New Challenge.","authors":"Daniel Wendling","doi":"10.1007/s40265-024-02100-w","DOIUrl":"https://doi.org/10.1007/s40265-024-02100-w","url":null,"abstract":"<p><p>Axial spondyloarthritis is a common form of chronic inflammatory rheumatic disease in adults, the treatment of which is based on non-pharmacological elements on the one hand, and pharmacological options on the other, such as non-steroidal anti-inflammatory drugs in the first line, followed by biological or targeted synthetic treatments. The therapeutic objective is remission or a low level of disease activity; if this objective is not achieved, the treatment is rotated or changed. Multiple changes is one factor illustrating the inability to achieve disease control and may lead to the notion of a difficult-to-treat disease (D2T). This requires a consensual definition including, beyond the number or therapeutic changes, the assessment of all the dimensions of the disease (objective signs of inflammation, residual pain, degenerative changes, psychosocial context). Recognising D2T patients will enable us to identify a particular population and the factors associated with this condition. When faced with a D2T disease, we need to analyse the causes of treatment failure and take into account the different components of the disease and the patient. In the absence of any prospect of new therapeutic targets in the short term for this disease, patient management may involve intensification of non-pharmacological means and evaluation of new therapeutic strategies such as combinations of targeted treatments.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460699","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":"Orexin Receptor Antagonists for the Prevention and Treatment of Alzheimer's Disease and Associated Sleep Disorders.","authors":"Matteo Carpi, Nicola Biagio Mercuri, Claudio Liguori","doi":"10.1007/s40265-024-02096-3","DOIUrl":"https://doi.org/10.1007/s40265-024-02096-3","url":null,"abstract":"<p><p>Orexins/hypocretins are neuropeptides produced by the hypothalamic neurons, binding two G-protein coupled receptors (orexin 1 and orexin 2 receptors) and playing a critical role in regulating arousal, wakefulness, and various physiological functions. Given the high prevalence of sleep disturbances in Alzheimer's disease (AD) and their reported involvement in AD pathophysiology, the orexin system is hypothesized to contribute to the disease pathogenesis. Specifically, recent evidence suggests that orexin's influence may extend beyond sleep regulation, potentially affecting amyloid-β and tau pathologies. Dual orexin receptor antagonists (DORAs), namely suvorexant, lemborexant, and daridorexant, demonstrated efficacy in treating chronic insomnia disorder across diverse clinical populations. Considering their stabilizing effects on sleep parameters and emerging evidence of a possible neuroprotective role, these agents represent a promising strategy for AD management. This leading article reviews the potential use of orexin receptor antagonists in AD, particularly focusing on their effect in modulating disease-associated sleep disturbances and clinical outcomes. Overall, clinical studies support the use of DORAs to enhance sleep quality in patients with AD with comorbid sleep and circadian sleep-wake rhythm disorders. Preliminary results also suggest that these compounds might influence AD pathology, potentially affecting disease progression. Conversely, research on selective orexin receptor antagonists in AD is currently limited. Further investigation is needed to explore orexin antagonism not only as a symptomatic treatment for sleep disturbances, but also for its broader implications in modifying AD neurodegeneration, emphasizing mechanisms of action and long-term outcomes.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371322","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}