Buprenorphine for Depression and Anxiety

描述（由申请人提供）：本研究项目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对抑郁症和焦虑症的开发。显然，医学上需要新的药物，以扩大治疗共病性抑郁和焦虑的选择，特别是对于大量对现有药物难治的患者。丁丙诺啡在医学上可获得并安全用于治疗对阿片类药物的身体依赖，但在非依赖人群中使用精神疾病方面几乎没有受到关注。丁丙诺啡作为一种mu-阿片受体（MOR）部分激动剂和kappa-阿片受体（KOR）拮抗剂，在药物奖励、身体依赖和镇痛模型中得到了广泛的研究。最近的研究强调了运动啡在应激中的作用，表明在动物模型中，KOR拮抗剂可以产生抗抑郁和抗焦虑作用。丁丙诺啡作为一种有效的more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作用的可能性。很少有关于丁丙诺啡在抑郁和焦虑动物模型中的作用的已发表的研究支持临床试验和开发或了解其潜在的作用机制。综上所述，这些实验将为考虑开发丁丙诺啡用于精神疾病的新适应症，并将其转化为治疗难治性抑郁和焦虑患者的前瞻性临床治疗研究奠定基础。

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.