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

被引：127

作者：

Carlezon, William A., Jr. ^{[1
]}

Beguin, Cecile ^{[2
]}

Knoll, Allison T. ^{[1
]}

Cohen, Bruce M. ^{[2
]}

机构：

[1] Harvard Univ, Sch Med, McLean Hosp, Behav Genet Lab,Dept Psychiat, Belmont, MA 02478 USA

[2] Harvard Univ, Sch Med, McLean Hosp, Mol Pharmacol Lab,Dept Psychiat, Belmont, MA 02478 USA

来源：

PHARMACOLOGY & THERAPEUTICS | 2009年 / 123卷 / 03期

基金：

美国国家卫生研究院;

关键词：

Depression; Antidepressant; Dynorphin; Kappa opioid; Dopamine; Model; Rat; Mouse; INTRACRANIAL SELF-STIMULATION; ELEMENT-BINDING PROTEIN; FORCED SWIM TEST; SALVINORIN-A; NOR-BINALTORPHIMINE; NUCLEUS-ACCUMBENS; RECEPTOR ANTAGONIST; SALVIA-DIVINORUM; DOPAMINERGIC-NEURONS; CREB PHOSPHORYLATION;

D O I：

10.1016/j.pharmthera.2009.05.008

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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 the 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 KOR 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. (C) 2009 Elsevier Inc. All rights reserved.

引用

页码：334 / 343

页数：10

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