Development of κ Opioid Receptor Antagonists

κ opioid receptors (KORs) belong to the G-protein-coupled class of receptors (GPCRs). They are activated by the endogenous opioid peptide dynorphin (DYN) and expressed at particularly high levels within brain areas implicated in modulation of motivation, emotion, and cognitive function. Chronic acti...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2013-03, Vol.56 (6), p.2178-2195
Main Authors: Carroll, F. Ivy, Carlezon, William A
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Clinical Trials as Topic
Drug Discovery - methods
Humans
Molecular Sequence Data
Peptides - chemistry
Peptides - pharmacology
Receptors, Opioid, kappa - antagonists & inhibitors
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Summary:κ opioid receptors (KORs) belong to the G-protein-coupled class of receptors (GPCRs). They are activated by the endogenous opioid peptide dynorphin (DYN) and expressed at particularly high levels within brain areas implicated in modulation of motivation, emotion, and cognitive function. Chronic activation of KORs in animal models has maladaptive effects including increases in behaviors that reflect depression, the propensity to engage in drug-seeking behavior, and drug craving. The fact that KOR activation has such a profound influence on behaviors often triggered by stress has led to interest in selective KOR antagonists as potential therapeutic agents. This Perspective provides a description of preclinical research conducted in the development of several different classes of selective KOR antagonists, a summary of the clinical studies conducted thus far, and recommendations for the type of work needed in the future to determine if these agents would be useful as pharmacotherapies for neuropsychiatric illness.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm301783x