δ opioid receptor

ZURICH, SWITZERLAND / ACCESSWIRE / October 21, 2024 / NLS Pharmaceutics Ltd. (NASDAQ:NLSP)(NASDAQ:NLSPW) (“NLS” or the “Company”), a Swiss clinical-stage biopharmaceutical company dedicated to developing therapies for rare and complex central nervous system disorders, is pleased to announce that its Japanese patent application No. 2020-513594 has been granted. The patent covers the use of Mazindol ER (extended-release) for the treatment of heroin dependence, providing a new therapeutic strategy for opioid use disorder. “The development of mazindol as a treatment for substance use disorder could represent a significant breakthrough, offering new hope for patients battling addiction. It is crucial we align our strategy with the evolving landscape of pharmaceutical innovation in this area.” said Alex Zwyer, Chief Executive Officer of NLSP. “This application highlights the continued commitment from NLS to pioneer therapeutic approaches to address significant unmet medical needs.” Key Highlights of this Patent Mazindol ER for Heroin Dependence : Mazindol, a tetracyclic compound with unique pharmacological properties, has shown promising in vivo results in reducing heroin dependence by modulating neurotransmitter systems involved in reward signaling and addiction pathways. The patent protects the use of Mazindol ER as a treatment for opioid addiction, specifically targeting heroin, one of the most potent and addictive opioids. Mechanism of Action : Unlike traditional opioid agonists and antagonists, Mazindol works by indirectly modulating the reward systems of the brain, targeting opioid receptors such as μ-opioid, κ-opioid, and δ-opioid receptors. By influencing these receptors, Mazindol reduces cravings and compulsive drug-seeking behaviors, helping to mitigate the effects of opioid use disorder without inducing the same level of dependence associated with other treatments. Focus on Long-Term Efficacy : The patent includes claims for the sustained-release formulation of Mazindol, which allows for a steady release of the drug over time, improving patient compliance and reducing the risk of relapse. This extended-release formulation is designed to maintain therapeutic levels of the drug in the bloodstream for prolonged periods, providing more consistent symptom management for individuals recovering from heroin addiction. Scientific Basis Opioid Use Disorder (OUD), particularly heroin addiction, poses a significant public health challenge worldwide. Heroin binds strongly to opioid receptors in the brain, leading to intense euphoria followed by physical dependence and withdrawal symptoms. Traditional treatments often rely on opioid substitution therapies, which can carry their own risks of dependence. Mazindol offers an innovative, non-opioid approach that addresses the brain’s addiction circuitry, potentially reducing the risk of relapse and improving recovery outcomes. The unique effect of Mazindol on heroin dependence lies in its ability to regulate the meso-corticolimbic system, which includes the ventral tegmental area (VTA) and nucleus accumbens-key regions in the brain’s reward circuitry. By normalizing these pathways, Mazindol helps reduce the compulsive behaviors associated with opioid use disorder, offering hope for individuals struggling with heroin addiction. Appeal Decision in Japan NLS Pharmaceutics successfully appealed the original rejection of its patent application, receiving a favorable decision from the Japan Patent Office (JPO) on October 2, 2024. The granted patent, which includes eight claims, provides robust protection for Mazindol ER and its specific use in treating opioid dependence, particularly heroin addiction. This decision reflects an innovative contribution to addiction medicine and positions Mazindol ER as a potentially transformative treatment for heroin dependence in Japan and beyond. About NLS Pharmaceutics Ltd. NLS Pharmaceutics Ltd. is a global development-stage biopharmaceutical company working with internationally recognized scientists and world-class partners to develop innovative therapies for patients with rare and complex central nervous system disorders. Headquartered in Switzerland and founded in 2015, NLS is led by an experienced management team with a track record of successfully developing and commercializing product candidates. For more information, visit . Safe Harbor Statement This press release contains forward-looking statements pursuant to U.S. Federal securities laws. For example, NLS discusses potential benefits of its products and the granted patent. Forward-looking statements are based on the current expectations of NLS management and are subject to numerous factors and uncertainties that could cause actual results to differ. These factors include technology changes, delays or obstacles in launching clinical trials, and the non-approval of NLS products by regulatory agencies. NLS undertakes no obligation to update any forward-looking statements to reflect events or circumstances after the date of this release unless required by law. Detailed risk information is included in NLS’s filings with the U.S. Securities and Exchange Commission (SEC), available at . Contact: Investor Relations Contact InvestorRelations@nls-pharma.com SOURCE: NLS Pharmaceutics AG View the original press release on accesswire.com

MONMOUTH JUNCTION, N.J.--( BUSINESS WIRE )--Tris Pharma, Inc. (Tris), a commercial-stage biopharmaceutical company focused on attention deficit hyperactivity disorder (ADHD), pain, addiction and neurological disorders, today announced that the company will present data from its first-in-class, late-stage investigational pain therapy with a novel mechanism of action, cebranopadol, at the upcoming International Association for the Study of Pain (IASP) 2024 World Congress on Pain, taking place August 5-9, 2024, in Amsterdam. “I am inspired to see the rise in interest, funding and research into the development of novel treatment options for the millions of people who suffer daily from debilitating pain that impacts their quality of life,” said Ketan Mehta, founder and CEO at Tris Pharma. “Our team has been working with urgency to advance cebranopadol, a first-in-class investigational pain therapy with a novel mechanism of action, through clinical studies with the goal of offering physicians an effective treatment option that they can confidently prescribe and patients feel is safe. We look forward to collaborating with the pain community at IASP 2024 and sharing our latest findings.” Cebranopadol is the first and only dual nociceptin/orphanin FQ peptide (NOP) receptor and µ-opioid peptide (MOP) receptor (dual-NMR) agonist in development to treat moderate-to-severe pain. Dual-NMR agonist compounds have the potential to deliver gold-standard pain relief with a strong safety profile because they mimic the body’s natural pain-modulation processes by synergizing the analgesic and safety characteristics of the NOP receptor with the analgesic advantages of the MOP receptor. Tris Pharma plans to share important news regarding its Phase 3 clinical trials in the near future. Symposium Highlighting Novel Pain Mechanism Tris Pharma will host a symposium featuring a series of presentations focused on dual-NMR agonists, a promising new mechanism of action in treating pain, and its potential to overcome the shortfalls of opioids for moderate-to-severe pain. The symposium will be presented as part of the congress by leading scientists with extensive experience in the research and development of novel pain therapies. Details of the symposium are as follows: Symposium: Break the Mold in Pain Biology: The Promise of a New Mechanism that May Overcome the Shortfalls of Current Moderate to Severe Pain Medications Presenters: Charles E. Argoff, MD, Albany Medical College; Roberto Ciccocioppo, PhD, University of Camerino; Jeffrey Gudin, MD, University of Miami Miller School of Medicine Location: RAI Amsterdam Convention Centre, Elicium I Date and Time: August 6, 12:45 – 1:45 p.m. CEST At IASP 2024 Tris Pharma will be present at Booth #316 where company executives will be available to provide additional information and data presented at the congress. About Cebranopadol (TRN-228) Cebranopadol is the first and only investigational dual nociceptin/orphanin FQ peptide (NOP) receptor and µ-opioid peptide (MOP) receptor (dual-NMR) agonist for the treatment of moderate-to-severe pain, as well as opioid use disorder (OUD). Cebranopadol offers a first of its kind and novel mechanism of action that takes advantage of the inherent properties of the NOP receptor, which has demonstrated both the potential to lessen the risk of misuse while still providing effective pain relief, and the potential to block drugs of abuse from producing drug-seeking behaviors. The FDA has granted Fast Track Designation to cebranopadol for chronic low back pain. Cebranopadol’s profile has been well-characterized in pain management studies, and if approved, it could become the first and only pain-relief therapy with the demonstrated ability to provide efficacy equivalent to opioids with significantly less risk for misuse or risk of physical dependence, addiction or overdose. About Tris Pharma Tris Pharma is a privately held, innovation-driven biopharmaceutical company that is applying its drug development capabilities and proprietary technologies to transform the treatment of ADHD, pain and neurological disorders, including addiction and diseases of the central nervous system. Tris is an established commercial organization with a robust portfolio of best-in-class ADHD products and a promising pipeline of differentiated, near-term drug candidates. More information is available at www.trispharma.com and on LinkedIn @ TrisPharma .

*仅供医学专业人士阅读参考科学家们已经反反复复验证过了，安慰剂是真有用。在临床研究中，安慰剂原本只是作为药物或者治疗方法的对照组，为患者提供“假”治疗。但是由于大脑强大的“暗示”功能，本该没有治疗作用的“药物”或者“治疗方法”也提供了一定的症状改善。也因此，研究人员认为实际治疗组也在一定程度上因为“安慰剂效应”获益。这就给临床治疗研究创造了新的困难。所以，除了感叹“安慰剂”的神奇作用，搞清楚其中的生物学机制也十分重要。北卡罗来纳大学教堂山分校的学者们选择了安慰剂的镇痛效用进行研究。通过结合小鼠行为试验，他们发现了安慰剂缓解疼痛的神经机制。研究表明，当小鼠预期自己的疼痛会得到缓解时，前扣带回皮质喙部-脑桥核（rACC→Pn）通路上的神经元活动增强，Pn神经元表达大量阿片类受体，引发安慰剂的镇痛作用。研究发表在《自然》杂志上。疼痛是一种主观体验，身心互动对疼痛感知有强大的影响力，受试者的积极预期可以在没有镇痛药物的情况下减少疼痛感知。安慰剂镇痛更是在医疗实践和临床试验中都起着非常重要的作用。研究人员设计了一个为期7天的安慰剂镇痛条件化模型（PAC）。模型由两个房间组成，在适应阶段（第1-3天），两个房间的地板为30℃，小鼠可以在房间内自由探索，以第3天表现为基线探索模式；条件化阶段（第4-6天），1号房间地板设置为48℃，2号房间温度保持不变，小鼠从1号房间进入2号房间，并建立“疼痛会缓解”的预期；测试阶段（第7天），两个房间地板均设置为48℃，评估“预期疼痛会缓解”可能引起的镇痛效果。小鼠条件化模型条件化小鼠表现出对2号房间的显著偏好，在2号房间里似乎变得“更不怕痛”，即使房间温度升高，也可以比在1号房间内坚持更久时间，才出现舔爪、抬腿、搔抓等因疼痛产生的伤害性行为，测试期间的整体伤害行为也较少。这种条件化诱导的镇痛效果持续时间长达一周。研究人员还发现，非条件化阶段进行阿片受体拮抗剂给药，会消除条件化产生的镇痛效果，暗示内源性阿片信号在安慰剂镇痛效果中发挥了关键作用。疼痛缓解预期过程中rACC→Pn神经元活动增强人类大脑成像研究表明，rACC与安慰剂镇痛效用有关。但是rACC的细胞类型众多，研究人员利用腺相关病毒标记条件化期间活跃的rACC神经元，发现rACC轴突投射集中在介导皮层-小脑交流的脑桥区域——脑桥核（Pn）。研究人员比较了小鼠在进行房间交换时的神经元活动。当小鼠有疼痛缓解预期时，rACC→Pn神经元活动增加；当小鼠无疼痛缓解预期时，神经元活动保持不变；当小鼠逐渐发现房间交换不能带来疼痛缓解（违背预期）时，rACC→Pn神经元活动显著减少。对rACC→Pn通路的光遗传学调控影响条件化诱导镇痛效果和疼痛行为脑片电生理学实验显示，在条件化过程中，rACC→Pn神经元的Ca2+活动增加，自发兴奋性突触后电流振幅增加，但是频率不变，神经元长期增强（LTP）增加。利用光激活和光抑制调控rACC→Pn通路活性，可以发现rACC→Pn参与了疼痛阈值的调节，即通路活性增加，则小鼠疼痛反应减弱，通路活性被抑制，小鼠疼痛反应增加。大量Pn神经元表达δ和μ阿片受体（分别为Oprd1和Oprm1），81%的Oprd1+Pn神经元表达兴奋性神经元标记。经过验证，研究人员证实Oprd1+Pn神经元与rACC的单突触连接，并且通过调节Oprd1+Pn神经元活性，可以调控安慰剂的镇痛效果。研究人员还研究了Pn神经元的主要靶点——小脑。通过标记Oprd1+Pn神经元在小脑中的投射，发现浦肯野细胞在条件化期间Ca2+活动显著增加，表现出与疼痛缓解预期相关的行为变化。疼痛是一种复杂的体验，包括感觉-辨别、情感-动机和认知-评价三个维度。研究揭示了安慰剂镇痛以及认知-评价维度的神经通路，更加完善了对疼痛的理解。同时，也开辟了通过激活rACC→Pn通路调控疼痛感知的可能性，为探究其他身心相互作用和安慰剂效应的神经通路提供了新的框架。参考文献：Chen C, Niehaus J K, Dinc F, et al. Neural circuit basis of placebo pain relief[J]. Nature, 2024: 1-3.本文作者丨王雪宁