Buprenorphine for Depression and Anxiety

丁丙诺啡治疗抑郁和焦虑

基本信息

批准号：
8239342
负责人：
IRWIN LUCKI
金额：
$ 40万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-04-01 至 2017-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8239342
关键词：
Absence of pain sensation Acute Agonist Animal Behavior Animal Model Animals Anti-Anxiety Agents Antidepressive Agents Anxiety Anxiety Disorders Area Attention Behavior Behavioral Brain Brain region Brain-Derived Neurotrophic Factor Buprenorphine C57BL/6 Mouse Chronic Clinical Clinical Research Clinical Treatment Clinical Trials Data Development Disease Dopamine Drug Interactions Dynorphins Effectiveness Foundations Genetic Genetic Models Goals Hippocampus (Brain)Inbred WKY Rats Ligands Major Depressive Disorder Medical Mental Depression Mental disorders Microdialysis Modeling Morbidity - disease rate Mus Nucleus Accumbens Opioid Opioid Receptor Patients Pattern Pharmaceutical Preparations Physical Dependence Population Public Health Publishing Rat Strains Rattus Refractory Research Resistance Role Screening procedure Sprague-Dawley Rats Stress Swimming Testing Therapeutic Translating approach behavior base behavior test clinical efficacy conventional therapy drug reward economic impact extracellular in vivo kappa opioid receptors mu opioid receptors neural circuit neurobehavioral neurogenesis pre-clinical programs prospective research study response social treatment effect

项目摘要

DESCRIPTION (provided by applicant): The overall goal of this research program is to evaluate the therapeutic potential for buprenorphine and to use animal studies to support its development for depression and anxiety disorders. There is a clear medical need for new drugs that would expand the options for treating comorbid depression and anxiety, especially for the substantial number of patients' refractory to current medications. Buprenorphine is medically available and used safely for the treatment of physical dependence to opioids but has received virtually no attention for the use of psychiatric disorders in nondependent populations. As a mu-opioid receptor (MOR) partial agonist and kappa-opioid receptor (KOR) antagonist, buprenorphine has been studied extensively in models of drug reward, physical dependence, and analgesia. Recent studies highlighting the role of dynorphin in stress have shown that KOR antagonists can produce antidepressant and anxiolytic effects in animal models. The pharmacological profile of buprenorphine as a potent MOR partial agonist and KOR antagonist supports the likelihood that buprenorphine would produce beneficial effects on stress-induced behaviors. Few published studies on the effects of buprenorphine in animal models of depression and anxiety exist to support clinical trials and development or to understand its potential mechanism of action. Taken together, these experiments will establish a basic foundation for considering the development of buprenorphine for new indications in psychiatric disorders and translate to prospective clinical treatment studies of depression and anxiety in treatment-resistant patients. PUBLIC HEALTH RELEVANCE: This project examines whether buprenorphine is likely to be effective for the clinical treatment of depression and anxiety disorders using preclinical animal behavior tests predictive of clinical activity. A neural circuitry model is proposed to explain the effectiveness of buprenorphine for treating psychiatric disorders. Major depression is an important public health problem because of its severe economic impact and contribution to morbidity from other medical disorders. Many patients do not respond to current medications. The results of this project will determine whether buprenorphine should be developed for the clinical treatment of comorbid depression and anxiety that is especially refractory to treatment with current medications.

描述（由申请人提供）：该研究计划的总体目标是评估丁丙诺啡的治疗潜力，并使用动物研究来支持其抑郁症和焦虑症的发展。明显的医疗需求需要新药，可以扩大治疗合并抑郁症和焦虑的选择，尤其是对于大量患者对当前药物的难治性。丁丙诺啡可在医学上获得，并安全地用于治疗对阿片类药物的物理依赖性，但几乎没有注意在非依赖性种群中使用精神疾病。作为一种MU-阿片受体（MOR）部分激动剂和Kappa-阿片受体（KOR）拮抗剂，丁丙诺啡已在药物奖励，身体依赖和镇痛模型中进行了广泛的研究。最近的研究强调了测能在压力中的作用，表明KOR拮抗剂可以在动物模型中产生抗抑郁和抗焦虑作用。丁丙诺啡作为一种有效的局部动力学和KOR拮抗剂的药理学特征支持丁丙诺啡会对压力引起的行为产生有益的影响的可能性。很少有关于丁丙诺啡在抑郁和焦虑模型中的影响的发表研究，以支持临床试验和发展或了解其潜在的作用机理。综上所述，这些实验将为考虑针对精神疾病的新适应症的开发而建立一个基本基础，并将其转化为对治疗耐药患者抑郁和焦虑的前瞻性临床治疗研究。公共卫生相关性：该项目检查丁丙诺啡是否可能使用临床前动物行为测试可预测临床活性的临床动物行为测试对抑郁症和焦虑症的临床治疗有效。提出了一种神经回路模型来解释丁丙诺啡对治疗精神疾病的有效性。重度抑郁症是一个重要的公共卫生问题，因为其经济严重影响和对其他医学疾病发病的贡献。许多患者对当前药物没有反应。该项目的结果将确定是否应开发丁丙诺啡来用于对合并症抑郁症和焦虑的临床治疗，这对于使用当前药物的治疗尤其令人难以忍受。