Kappa-opioid ligands in the study and treatment of mood disorders.

Kappa-opioid ligands in the study and treatment of mood disorders.
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DOI:
10.1016/j.pharmthera.2009.05.008
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发表时间:
2009-09
影响因子:
13.5
通讯作者:
Cohen BM
Cohen BM
中科院分区:
医学1区
文献类型:
--
作者:
Carlezon WA Jr;Béguin C;Knoll AT;Cohen BM

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情绪的生物学基础尚不清楚。大多数关于情绪和情感状态的研究都集中在含有单胺的大脑系统的作用上(例如,多巴胺、去甲肾上腺素、血清素)。然而,越来越清楚的是,大脑中的内源性阿片系统也可能参与情绪调节。在这篇综述中,我们集中在κ-阿片受体(KOR)配体在精神疾病的研究和治疗的潜在效用。我们小组和其他人的研究表明,KOR拮抗剂可能对抑郁症有用,KOR激动剂可能对躁狂症有用,KOR部分激动剂可能对情绪稳定有用。目前可用的药物具有一些不利的性质,可以通过药物化学来解决。开发具有改善的药物样特征的KOR选择性药物将促进临床前和临床研究,这些研究旨在评估KOR作为新药可行靶点的可能性。
The biological basis of mood is not understood. Most research on mood and affective states has focused on the roles of brain systems containing monoamines (e.g., dopamine, norepinephrine, serotonin). However, it is becoming clear that endogenous opioid systems in the brain may also be involved in regulation of mood. In this review, we focus on the potential utility of kappa-opioid receptor (KOR) ligands in the study and treatment of psychiatric disorders. Research from our group and others suggests that KOR antagonists might be useful for depression, KOR agonists might be useful for mania, and KOR partial agonists might be useful for mood stabilization. Currently available agents have some unfavorable properties that might be addressed through medicinal chemistry. The development of KOR-selective agents with improved drug-like characteristics would facilitate preclinical and clinical studies designed to evaluate the possibility that KORs are a feasible target for new medications.
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