Journal
AAPS JOURNAL
Volume 11, Issue 2, Pages 312-322Publisher
SPRINGER
DOI: 10.1208/s12248-009-9105-4
Keywords
antidepressant; blood-brain barrier; cocaine abuse; dynorphin analogs; peptide metabolism
Categories
Funding
- National Institute on Drug Abuse [R01 DA018832, R01 DA023924, K02 DA000393]
- State of Florida, Executive Office of the Governor's Office of Tourism, Trade, and Economic Development
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While narcotic analgesics such as morphine, which act preferentially through mu opioid receptors, remain the gold standard in the treatment of severe pain, their use is limited by detrimental liabilities such as respiratory depression and drug dependence. Thus, there has been considerable interest in developing ligands for kappa opioid receptors (KOR) as potential analgesics and for the treatment of a variety of other disorders. These include effects mediated both by central receptors, such as antidepressant activity and a reduction in cocaine-seeking behavior, and activity resulting from the activation of peripheral receptors, such as analgesic and anti-inflammatory effects. While the vast majority of opioid receptor ligands that have progressed in preclinical development have been small molecules, significant advances have been made in recent years in identifying opioid peptide analogs that exhibit promising in vivo activity. This review will focus on possible therapeutic applications of ligands for KOR and specifically on the potential development of peptide ligands for these receptors.
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