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

• 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
• 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

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用于研究和治疗疼痛、抑郁、焦虑以及疼痛和情感障碍的共病病例。最近的证据表明，慢性疼痛和精神疾病之间存在显著的相互作用。特别是，慢性疼痛（如纤维肌痛、慢性下背痛、膀胱疼痛综合征）似乎在流行病学和生物学上与重度抑郁症（MDD）有关。慢性疼痛患者中MDD或抑郁/焦虑症状的发生率非常高。在这种情况下，这两种不同的疾病实际上相互增强，创造了一个非常危险的病理环境。有趣的是，这种重叠为患者的治疗提供了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都有效的治疗方法。这种情况将是双重有利的，因为它可以在单一疾病的早期阶段用作预防性治疗，以防止继发性疾病（即疼痛或抑郁）的发展。我们的目的是测试的假设，疼痛和抑郁症的共同机制，可用于针对这些疾病的新化合物针对血清素G蛋白偶联受体（GPCR）。5-羟色胺是一种脑神经化学物质，5-羟色胺受体是精神疾病中最常见的靶点之一，最近在慢性疼痛障碍中也是如此。然而，大多数使用阿托宁靶向药物的研究都使用了最初筛选为抗抑郁药或镇痛药的既定药物，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它们的共病慢性疼痛和抑郁/焦虑来提高我们的化合物成功的可能性。我们将测试提取物，馏分，和纯化 这些化合物来自先前在巴拿马高度生物多样性的沃茨收集的海洋蓝细菌。从海洋环境中发现天然产物是一个相当新的研究领域，但已经在各种疾病领域产生了大量有趣和重要的化合物。主要的研究集中在发现毒性化合物作为抗菌剂、抗真菌剂或抗癌剂的效用上。然而，这项建议将检查海洋蓝藻提取物的能力，以调节血清素GPCR，治疗疼痛和抑郁症，使用体内小鼠模型后，对GPCR的提取物的初步筛选。