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Buprenorphine for Depression and Anxiety

丁丙诺啡治疗抑郁和焦虑

基本信息

批准号：
8451367
负责人：
IRWIN LUCKI
金额：
$ 38.4万
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/8451367
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 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 screening 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.

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，并利用动物研究来支持其治疗抑郁症和焦虑症的开发。显然，医学上需要新药来扩大治疗抑郁症和焦虑症共病的选择，特别是对于大量对当前药物耐药的患者。丁丙诺啡在医学上是可用的，并且可以安全地用于治疗对阿片类药物的身体依赖，但在非依赖性人群中使用丁丙诺啡来治疗精神疾病几乎没有受到关注。作为 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赏、身体依赖性和镇痛模型中得到广泛研究。最近强调强啡肽在应激中的作用的研究表明，KOR 拮抗剂可以在动物模型中产生抗抑郁和抗焦虑作用。丁丙诺啡作为有效的 MOR 部分激动剂和 KOR 拮抗剂的药理学特征支持丁丙诺啡对应激诱导行为产生有益影响的可能性。很少有关于丁丙诺啡在抑郁和焦虑动物模型中的影响的已发表的研究来支持临床试验和开发或了解其潜在的作用机制。总而言之，这些实验将为考虑开发丁丙诺啡用于精神疾病新适应症奠定基础，并转化为针对难治性患者抑郁和焦虑的前瞻性临床治疗研究。