期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 59, 期 15, 页码 7011-7028出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.5b01499
关键词
-
资金
- National Institutes of Health [R01DA014026, R01DA027811, R43NS070664, R43HL115984]
In the two decades since the discovery of the nociceptin opioid receptor (NOP) and its ligand, nociceptin/orphaninFQ (N/OFQ), steady progress has been achieved in understanding the pharmacology of this fourth opioid receptor/peptide system, aided by genetic and pharmacologic approaches. This research spawned an explosion of small molecule NOP receptor ligands from discovery programs in major pharmaceutical companies. NOP agonists have been investigated for their efficacy in preclinical models of anxiety, cough, substance abuse, pain (spinal and peripheral), and urinary incontinence, whereas NOP antagonists have been investigated for treatment of pain, depression, and motor symptoms in Parkinson's disease. Translation of preclinical findings into the clinic is guided by PET and receptor occupancy studies, particularly for NOP antagonists. Recent progress in preclinical NOP research suggests that NOP agonists may have clinical utility for pain treatment and substance abuse pharmacotherapy. This review discusses the progress toward validating the NOP-N/OFQ system as a therapeutic target.
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