Kappa-opioid ligands in the study and treatment of mood disorders.
Carlezon WA Jr, B├ęguin C, Knoll AT, Cohen BM.
Behavioral Genetics Laboratory,
Department of Psychiatry, Harvard Medical School,
McLean Hospital, Belmont MA 02478
Pharmacol Ther. 2009 Jun 1.


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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