Cyanobacterial Natural Products to Treat Comorbid Pain and Depression

蓝藻天然产物可治疗共病疼痛和抑郁症

基本信息

批准号：
8753582
负责人：
BENEDICT J KOLBER
金额：
$ 39.28万
依托单位：
DUQUESNE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-07-01 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8753582
关键词：
Address Affective Affective Symptoms Affinity Analgesics Animal Model Animals Anti-Anxiety Agents Anti-Bacterial Agents Antidepressive Agents Antifungal Agents Antineoplastic Agents Anxiety Area Behavior Behavioral Binding Biological Assay Biological Factors Biological Sciences Brain Chemicals Chromatography Chronic low back pain Collaborations Collection Comorbidity Complex Mixtures Crude Extracts Cyanobacterium Data Development Disease Effectiveness Environment Exhibits Fibromyalgia Fractionation G-Protein-Coupled Receptors General Population Grant High Pressure Liquid Chromatography Hypersensitivity Incidence Injury Interdisciplinary Study Interstitial Cystitis Ligands Link Maintenance Major Depressive Disorder Marines Medical Mental Depression Mental disorders Mentors Mentorship Modeling Molecular Mus National Institute of Mental Health Natural Products Chemistry Neuropathy Nuclear Magnetic Resonance Pain Pain Disorder Panama Patients Pharmaceutical Preparations Pharmacologic Substance Poison Preclinical Drug Evaluation Principal Investigator Prophylactic treatment Psychotropic Drugs Quality of life Research Research Personnel Science Serotonin Serotonin Receptor 5-HT2C Signal Transduction Staging Structure Symptoms System Tail Suspension Techniques Testing Therapeutic Water Work behavior change chronic depression chronic pain depressive symptoms effective therapy experience improved in vivo interest marine natural product mouse model nerve injury neurochemistry novel painful neuropathy preference prevent professor programs public health relevance receptor research study screening serotonin receptor silochrome spontaneous pain success therapy development tool

项目摘要

DESCRIPTION (provided by applicant): This proposal will look to use novel natural products for the study and treatment of pain, depression, anxiety, and comorbid instances of pain and affective disturbances. Recent evidence demonstrates a significant interaction between chronic pain and psychiatric illness. In particular, chronic pain (e.g. fibromyalgia, chronic lower back pain, painful bladder syndrome) seems to be linked both epidemiologically and biologically with major depressive disorder (MDD). Rates of MDD or depressive/anxiety symptoms in chronic pain patients are very high. In this situation, the two separate diseases actually potentiate one another to create an acutely dangerous pathological environment. Interestingly, this overlap presents an important new mechanistic and therapeutic avenue for the treatment of patients. That is, these common mechanisms might be useful for the development of treatments that show efficacy against both diseases with a single agent. This scenario would be doubly advantageous in that it could be used as a prophylactic treatment in the early stages of a single disorder to prevent the development of the secondary disease (i.e. pain or depression). We aim to test the hypothesis that the common mechanisms of pain and depression can be used to target these disorders with novel compounds directed at serotonin G-protein coupled receptors (GPCRs). Serotonin is a brain neurochemical and serotonin receptors are one of the most common targets in psychiatric disease and more recently in chronic pain disorders. Most studies using serotonin-targeting agents, however, have used established drugs that were originally screened as either antidepressive OR analgesic agents, not both. We aim to improve the likelihood of success of our compounds by testing them for comorbid chronic pain and depression/anxiety during the initial testing. We will be testing extracts, fractions, and purified compounds from marine cyanobacteria previously collected in the highly biodiverse waters of Panama. The discovery of natural products from the marine environment is a fairly recent field of research but has yielded a large number of interesting and important compounds in a variety of disease areas. Predominately studies have focused on the discovery of toxic compounds for their utility as anti-bacterial, anti-fungal, or anti-cancer agents. This proposal, however, will examine extracts from marine cyanobacteria for their ability to modulate serotonin GPCRs, to treat pain and depression, using in vivo mouse models following initial screening of the extracts against GPCRs.

描述（由申请人提供）：该提案将寻求使用新型天然产品来研究和治疗疼痛、抑郁、焦虑以及疼痛和情感障碍的共病情况。最近的证据表明慢性疼痛和精神疾病之间存在显着的相互作用。特别是，慢性疼痛（例如纤维肌痛、慢性腰痛、膀胱疼痛综合征）似乎在流行病学和生物学上都与重度抑郁症（MDD）有关。慢性疼痛患者出现抑郁症或抑郁/焦虑症状的比例非常高。在这种情况下，这两种不同的疾病实际上会相互增强，从而创造出一种极其危险的病理环境。有趣的是，这种重叠为患者的治疗提供了一种重要的新机制和治疗途径。也就是说，这些共同的机制可能有助于开发用单一药物对两种疾病均有效的治疗方法。这种情况将具有双重优势，因为它可以用作单一疾病早期阶段的预防性治疗，以防止继发性疾病（即疼痛或抑郁）的发展。我们的目的是测试这样一个假设：疼痛和抑郁的常见机制可用于通过针对血清素 G 蛋白偶联受体 (GPCR) 的新型化合物来治疗这些疾病。血清素是一种大脑神经化学物质，血清素受体是精神疾病以及最近慢性疼痛疾病中最常见的靶标之一。然而，大多数使用血清素靶向药物的研究所使用的药物最初被筛选为抗抑郁药或镇痛药，而不是两者兼而有之。我们的目标是通过在初始测试期间测试化合物的共病慢性疼痛和抑郁/焦虑来提高化合物成功的可能性。我们将测试提取物、级分和纯化的来自先前在巴拿马高度生物多样性水域中收集的海洋蓝藻化合物。从海洋环境中发现天然产物是一个相当新的研究领域，但在各种疾病领域已经产生了大量有趣且重要的化合物。主要研究集中于发现有毒化合物作为抗菌剂、抗真菌剂或抗癌剂。然而，该提案将在对提取物针对 GPCR 进行初步筛选后，使用体内小鼠模型来检查海洋蓝藻提取物调节血清素 GPCR 、治疗疼痛和抑郁的能力。