Sertraline Citrate

*仅供医学专业人士阅读参考没想到有一天，抗生素竟然遭到了非抗生素的“背刺”。近期，马萨诸塞大学医学院Amir Mitchell团队发表了一项重要研究成果，他们在分析了186种抗生素和非抗生素药物后发现，非抗生素与抗生素之间很多时候呈正交关系，即它们通过不同的机制作用于细菌。值得注意的是，药物输送相关基因的分析显示，虽然非抗生素与抗生素对细菌的作用机制不同，但他们却都受到了细菌外排（细菌耐药的一个重要机制）的影响。这也就意味着，细菌在对非抗生素产生耐药性的同时，也会不小心引发抗生素交叉耐药。研究发表在顶级期刊《科学》上。论文首页截图抗生素耐药是全球健康的最大问题之一，据估计，到2050年，每年将会有1000万人死于耐药性感染。更让人头疼的是，从1990年以来，人类发现新的抗生素种类相当有限。而近年来，非抗生素展现出的抗菌活性让人们看到了新的希望。然而更大的问题是，我们对非抗生素的抗菌活性还存在很多未知，比如非抗生素是如何作用于细菌的，是否和抗生素一样？它是否会导致细菌耐药？等等，总之这些问题都有待解答。Amir Mitchell团队为了搞清楚非抗生素作用于细菌的机制，他们选取了1280种药物，这些药物包括市面上已经获批了的，还有一些是正在研发中的药物，其中226种为抗生素，1054种为非抗生素。通过观察每个药物对大肠杆菌的影响，研究人员最终选取了186种可以显著抑制大肠杆菌生长的药物（103种抗生素和83种非抗生素）。药物筛选接下来，研究人员想知道，非抗生素的抑菌作用是否可以归咎于与抗生素有着一致的化学相似性。通过计算Tanimoto系数（0.8以上就是高度相似了），研究人员发现，同类抗生素，即对细菌有着相同作用机制的抗生素们通常具有很高的化学相似性，但不同类型的抗生素、抗生素和非抗生素，以及非抗生素之间化学相似性较低。这一发现表明，非抗生素显示出的抗菌活性，并不能归咎于它们在化学特征上类似于抗生素，而更可能是它们通过不同的机制来抑制细菌生长。随后，研究人员利用混合基因筛选方法捕获了90种抗生素对细菌的作用机制，并生成了针对抗生素的药物相关性网络。在将非抗生素加入到抗生素的药物相关性网络中后，研究人员发现，非抗生素与抗生素之间呈正交关系，也就是说，大多数非抗生素与抗生素作用机制的确不同（如果存在一样的机制，网络模块会聚集在一起）。药物相关性网络不过意外的是，一些非抗生素之间却存在相关性。于是研究人员又构建了非抗生素的药物相关性网络，结果共发现九个独立的网络模块，共涉及如生物合成和代谢过程，脂多糖生物合成相关的过程等多种生物功能。接下来，研究人员观察了一些参与细菌膜通透性和转运的基因对药物抗菌活性的影响，结果发现删除细菌的某些基因会增加药物的敏感性（尤其是一些编码抗性-结瘤-分裂家族转运蛋白、Tol-Pal系统和外膜蛋白的基因）。敲除编码膜通透性和转运的基因，会增加抗生素和非抗生素的抗菌活性此外，研究还发现，有26种包括抗生素和非抗生素在内药物都会受到五种或更多不同转运系统的影响。根据以上结果，研究人员推测，尽管大多数非抗生素与抗生素作用机制不同，但若因为非抗生素相关膜通透性和转运途径导致的耐药，那么细菌也可能通过同样途径对抗生素产生耐药。为了证明这一猜想，研究人员打算做一个药物抗性演化实验。研究人员从非抗生素的药物相关性网络的不同模块中选取了链脲佐菌素（Streptozotocin）、三氯苯达唑（Triclabendazole）和舍曲林（sertraline）这三种非抗生素，并将其放置于5种独立进化的大肠杆菌中。结果发现，对链脲佐菌素、三氯苯达唑适应的演化细菌完全耐药，而对舍曲林适应的演化细菌竟然增加了两倍以上的抗药性。通过对演化细菌进行基因组测序，研究人员发现了三种的非抗生素导致细菌耐药的机制。对链脲佐菌素耐药的细菌进化出了让nagE基因失活（这一基因编码葡萄糖-6－磷酸运输体，负责把药物运输到细菌内）的本事，总结就是谁都别想进来。对三氯苯达唑耐药的细菌让编码翻译起始因子IF2的基因突变了（非抗生素可与IF2结合可组织细菌蛋白质生成），总结就是细菌换了个锁芯，主打一个让你有钥匙也打不开。对舍曲林耐药的细菌让调节外排泵的基因（marR、acrR和lon）发生了突变，增加了多种外排途径，总结就是谁来都得给撵出去。鉴于细胞外排也是细菌对抗生素耐药的主要机制，研究人员认为对舍曲林耐药细菌也可能无意间促进了其对抗生素的耐药（围绕舍曲林耐药菌的抗生素耐药性实验也证实了这一点）。这就好比抗生素和细菌要打架，非抗生素巴巴地冲过去给细菌送了一份装备经验大礼包，这让抗生素怎么玩，纯纯背刺。总之，该研究通过遗传筛选和网络分析，发现一些非抗生素药物可能存在与抗生素不同的抑菌机制，这为开发新型抗菌药物提供了新的方向。不过在抗生素使用过程中导致的抗生素耐药也是一个亟须关注的问题。 参考文献：[1]Guillen M N, Li C, Rosener B, et al. Antibacterial activity of nonantibiotics is orthogonal to standard antibiotics[J]. Science, 2024: eadk7368.本文作者丨张金旭

DUBLIN, July 26, 2023 /PRNewswire/ -- The "Obsessive-Compulsive Disorder (OCD) Market Insights, Epidemiology, and Forecast to 2032" report has been added to ResearchAndMarkets.com's offering. Obsessive-Compulsive Disorder (OCD) Market: In-Depth Analysis and Treatment Landscape Obsessive-Compulsive Disorder (OCD) is a mental health disorder characterized by intrusive thoughts, images, or impulses causing anxiety, and repetitive behaviors aimed at reducing that anxiety. It follows a chronic course, often leading to years of suffering before seeking treatment. The DSM-5 diagnostic criteria for OCD remain largely unchanged from DSM-IV, with two specifiers added: insight and tic-related disorder. Market Overview: In 2022, there were approximately 12,082,000 total prevalent cases of OCD in the 7 major markets (7MM). Most diagnosed cases are severe, with 50% classified as severe, 35% as moderate, and 15% as mild. The United States accounted for the highest number of diagnosed cases in 2022, approximately 2,156,000 cases, and the OCD market size in the US was around USD 600 million. Treatment Landscape: Treatment for OCD involves building a therapeutic alliance, psychoeducation, and utilizing psychological and/or pharmacological approaches. Selective Serotonin Reuptake Inhibitors (SSRIs) are the most commonly prescribed medications for OCD, with drugs like sertraline, fluoxetine, and fluvoxamine being popular choices. Emerging Therapies: Troriluzole, developed by Biohaven Pharmaceuticals, is a promising drug in the OCD treatment landscape. It is a glutamate-release inhibitor and has shown encouraging results in clinical trials. If successful, troriluzole is expected to bring major changes in the OCD treatment landscape, offering safer and more effective options. Market Outlook: The total market size of OCD in the 7MM is projected to increase at a CAGR of ~5%, reaching approximately USD 1,000 million by 2032. The growth is driven by an increase in the prevalent pool of the disease and the launch of new therapies. Key Highlights: Obsessive-compulsive disorder (OCD) has been given increased attention in DSM-5, receiving its chapter. However, the diagnostic criteria for OCD in DSM-5 remain largely the same as in DSM-IV, requiring either obsessions or compulsions. The major change in the DSM-5 criteria for OCD is the addition of two specifiers for this diagnosis: insight and tic-related disorder. OCD symptoms may be present for years before treatment is sought, and those affected often suffer in silence. The disease follows a chronic waxing and waning course where 15% of patients have deterioration, and 5% have episodes with inter-episode recovery. The diagnosis of obsessive-compulsive disorder (OCD) is established by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnostic criteria, while the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) is used for the assessment of its severity. In 2022, there were ~12,082,000 total prevalent cases of obsessive-compulsive disorder (OCD) in the 7MM. Most of the diagnosed cases of Obsessive Compulsive Disorder (OCD) are severe, with around 15%, 35%, and 50% of individuals having mild, moderate, and severe OCD, respectively. The United States accounted for the highest number of diagnosed cases of OCD in the 7MM, i.e., ~2,156,000 cases in 2022. In 2022, the market size of OCD was the highest in the US among the 7MM, accounting for approximately USD 600 million. Treatment of OCD comprises several components, starting with building a therapeutic alliance with the patient and psychoeducation. Then psychological and/or pharmacological approaches, and, for patients with treatment-resistant OCD, neuromodulation, and neurosurgery. The NICE guidelines propose CBT as the treatment of choice for OCD and body dysmorphic disorder due to the rigorous research invested into CBT for OCD and the effectiveness of treatment. The expected launch of troriluzole (Biohaven Pharmaceuticals) by 2027 is set to bring major changes in the treatment landscape of OCD, bringing in safer and more effective treatment options for OCD patients. Selective Serotonin Reuptake Inhibitors (SSRIs) are the most popular form of treatment for OCD, which works by increasing serotonin levels in the brain. Some widely used medications for the treatment of OCD are citalopram (CELEXA, CIPRAMIL), escitalopram (CIPRALEX, LEXAPRO), fluoxetine (PROZAC), fluvoxamine (FAVERIN, LUVOX), paroxetine (PAXIL, SEROXAT), sertraline (LUSTRAL, ZOLOFT). If these medications fail to work, a non-selective SRI may be prescribed. However, because it affects neurotransmitters in the brain other than just serotonin, there are more side effects, and therefore it is usually not a first-choice medication for treating OCD. The non-selective SRI most commonly used for treating OCD is clomipramine (ANAFRANIL). The generic alternatives of the approved marketed assets for OCD, such as sertraline hydrochloride, fluoxetine, fluvoxamine, clomipramine, etc., entered the market from 1996-2006. Key Topics Covered 1. Key Insights 2. Report Introduction 3. OCD Market Overview at a Glance 4. Executive Summary of Obsessive-compulsive Disorder (OCD) 5. Epidemiology and Market Methodology 6. Disease Background and Overview 7. Epidemiology and Patient Population 8. Patient Journey 9. Marketed Therapies 10. Emerging Therapies 11. OCD: The 7MM Market Analysis 12. KOL Views 13. SWOT Analysis 14. Unmet needs 15. Market Access and Reimbursement 16. Appendix For more information about this report visit About ResearchAndMarkets.com ResearchAndMarkets.com is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends. Media Contact: Research and Markets Laura Wood, Senior Manager [email protected] For E.S.T Office Hours Call +1-917-300-0470 For U.S./CAN Toll Free Call +1-800-526-8630 For GMT Office Hours Call +353-1-416-8900 U.S. Fax: 646-607-1904 Fax (outside U.S.): +353-1-481-1716 Logo: SOURCE Research and Markets