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）：该提案将使用新颖的天然产品来研究和治疗疼痛，抑郁，焦虑和合并症的疼痛和情感障碍实例。最近的证据表明，慢性疼痛与精神病之间存在显着相互作用。特别是，慢性疼痛（例如纤维肌痛，慢性下背部疼痛，疼痛的膀胱综合征）似乎在流行病学和生物学上与主要抑郁症（MDD）联系在一起。慢性疼痛患者中MDD或抑郁/焦虑症状的发生率很高。在这种情况下，两种单独的疾病实际上相互增强，以创造出急性危险的病理环境。有趣的是，这种重叠是一种重要的新机械和治疗途径，用于治疗患者。也就是说，这些常见机制可能对与单一药物相对的疾病的疗法的发展可能有用。这种情况将是双重有利的，因为它可以在单个疾病的早期阶段用作预防性治疗，以防止继发性疾病的发展（即疼痛或抑郁症）。我们旨在检验以下假设：疼痛和抑郁的常见机制可用于用针对5-羟色胺G蛋白偶联受体（GPCR）的新型化合物（GPCR）来靶向这些疾病。 5-羟色胺是一种脑神经化学，5-羟色胺受体是精神病中最常见的靶标之一，最近在慢性疼痛障碍中。然而，大多数使用5-羟色胺靶向剂的研究都使用了最初被筛查为抗抑郁剂或镇痛药的已建立药物，而不是两者兼而有之。我们旨在通过在初次测试期间对化合物的慢性疼痛和抑郁/焦虑进行测试，以提高化合物成功的可能性。我们将测试提取物，分数和纯化先前在巴拿马高度生物多样水域收集的海洋蓝细菌的化合物。从海洋环境中发现天然产品是一个相当近期的研究领域，但在各种疾病地区产生了许多有趣而重要的化合物。主要的研究集中于发现有毒化合物，以作为抗菌，抗真菌或抗癌药的效用。但是，该提案将检查海洋蓝细菌中的提取物，以调节5-羟色胺GPCR，治疗疼痛和抑郁症的能力，在对GPCR进行初次筛选后使用体内小鼠模型。