Abstract:
:Misuse of prescription opioids, opioid addiction, and overdose underscore the urgent need for developing addiction-free effective medications for treating severe pain. Mu opioid peptide (MOP) receptor agonists provide very effective pain relief. However, severe side effects limit their use in the clinical setting. Agonists of the nociceptin/orphanin FQ peptide (NOP) receptor have been shown to modulate the antinociceptive and reinforcing effects of MOP agonists. We report the discovery and development of a bifunctional NOP/MOP receptor agonist, AT-121, which has partial agonist activity at both NOP and MOP receptors. AT-121 suppressed oxycodone's reinforcing effects and exerted morphine-like analgesic effects in nonhuman primates. AT-121 treatment did not induce side effects commonly associated with opioids, such as respiratory depression, abuse potential, opioid-induced hyperalgesia, and physical dependence. Our results in nonhuman primates suggest that bifunctional NOP/MOP agonists with the appropriate balance of NOP and MOP agonist activity may provide a dual therapeutic action for safe and effective pain relief and treating prescription opioid abuse.
journal_name
Sci Transl Medjournal_title
Science translational medicineauthors
Ding H,Kiguchi N,Yasuda D,Daga PR,Polgar WE,Lu JJ,Czoty PW,Kishioka S,Zaveri NT,Ko MCdoi
10.1126/scitranslmed.aar3483subject
Has Abstractpub_date
2018-08-29 00:00:00issue
456eissn
1946-6234issn
1946-6242pii
10/456/eaar3483journal_volume
10pub_type
杂志文章abstract::The August 2011 Clinical and Translational Science Awards conference "Using IT to Improve Community Health: How Health Care Reform Supports Innovation" convened four "Think Tank" sessions. Thirty individuals, representing various perspectives on community engagement, attended the "Health information technology (HIT) a...
journal_title:Science translational medicine
pub_type:
doi:10.1126/scitranslmed.3003363
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abstract::Direct-to-consumer (DTC) advertising of suspect goods and services has burgeoned because of the Internet. Despite very limited approval for use, DTC stem cell-marketed "treatments" have emerged for an array of conditions, creating global public health and safety risks. However, it remains unclear whether such use of s...
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pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2016-06-22 00:00:00
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更新日期:2010-01-06 00:00:00
abstract::High doses of oral vitamin D3 attenuate skin inflammation following experimentally induced sun damage. ...
journal_title:Science translational medicine
pub_type: 评论,杂志文章
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doi:10.1126/scitranslmed.aac7019
更新日期:2015-10-21 00:00:00
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pub_type: 杂志文章,随机对照试验
doi:10.1126/scitranslmed.aar3752
更新日期:2018-05-23 00:00:00
abstract::Attention deficit hyperactivity disorder (ADHD) is a common and persistent condition characterized by developmentally atypical and impairing inattention, hyperactivity, and impulsiveness. We identified de novo and rare copy number variations (CNVs) in 248 unrelated ADHD patients using million-feature genotyping arrays...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3002464
更新日期:2011-08-10 00:00:00
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更新日期:2017-10-04 00:00:00
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doi:10.1126/scitranslmed.3006200
更新日期:2013-08-07 00:00:00
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pub_type: 杂志文章
doi:10.1126/scitranslmed.3006277
更新日期:2013-07-10 00:00:00
abstract::Because of the well-established therapeutic benefit of boosting antitumor responses through blockade of the T cell inhibitory receptor PD-1, it has been proposed that PD-1 blockade could also be useful in infectious disease settings, including Mycobacterium tuberculosis (Mtb) infection. However, in preclinical models,...
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更新日期:2019-01-16 00:00:00
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pub_type: 杂志文章,评审
doi:10.1126/scitranslmed.3002804
更新日期:2011-09-28 00:00:00
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journal_title:Science translational medicine
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更新日期:2012-09-05 00:00:00
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更新日期:2017-02-01 00:00:00
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pub_type: 杂志文章,随机对照试验
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更新日期:2014-01-08 00:00:00
abstract::Parenteral and oral routes have been the traditional methods of administering cytotoxic agents to cancer patients. Unfortunately, the maximum potential effect of these cytotoxic agents has been limited because of systemic toxicity and poor tumor perfusion. In an attempt to improve the efficacy of cytotoxic agents whil...
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abstract::Stimulator of interferon genes (STING) is a cytosolic receptor that senses both exogenous and endogenous cytosolic cyclic dinucleotides (CDNs), activating TBK1/IRF3 (interferon regulatory factor 3), NF-κB (nuclear factor κB), and STAT6 (signal transducer and activator of transcription 6) signaling pathways to induce r...
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更新日期:2015-04-15 00:00:00
abstract::Patients undergoing surgical resection of primary breast tumors confront a risk for metastatic recurrence that peaks sharply 12 to 18 months after surgery. The cause of early metastatic relapse in breast cancer has long been debated, with many ascribing these relapses to the natural progression of the disease. Others ...
journal_title:Science translational medicine
pub_type: 杂志文章
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更新日期:2018-04-11 00:00:00