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.
机构:
Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Sch Med, Richmond, VA USA
Inst Anim Care & Use Comm, Memphis, TN USAVirginia Commonwealth Univ, Dept Pharmacol & Toxicol, Sch Med, Richmond, VA USA
Banks, Matthew L.
;
Czoty, Paul W.
论文数: 0引用数: 0
h-index: 0
机构:
Inst Anim Care & Use Comm, Memphis, TN USA
Wake Forest Sch Med, Dept Physiol & Pharmacol, Winston Salem, NC USAVirginia Commonwealth Univ, Dept Pharmacol & Toxicol, Sch Med, Richmond, VA USA
Czoty, Paul W.
;
Negus, Sidney S.
论文数: 0引用数: 0
h-index: 0
机构:
Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Sch Med, Richmond, VA USA
Inst Anim Care & Use Comm, Memphis, TN USAVirginia Commonwealth Univ, Dept Pharmacol & Toxicol, Sch Med, Richmond, VA USA
机构:
Harvard Univ, McLean Hosp, Sch Med, Alcohol & Drug Abuse Res Ctr, Belmont, MA 02478 USAHarvard Univ, McLean Hosp, Sch Med, Alcohol & Drug Abuse Res Ctr, Belmont, MA 02478 USA
Bowen, CA
;
Fischer, BD
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h-index: 0
机构:
Harvard Univ, McLean Hosp, Sch Med, Alcohol & Drug Abuse Res Ctr, Belmont, MA 02478 USAHarvard Univ, McLean Hosp, Sch Med, Alcohol & Drug Abuse Res Ctr, Belmont, MA 02478 USA
Fischer, BD
;
Mello, NK
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, McLean Hosp, Sch Med, Alcohol & Drug Abuse Res Ctr, Belmont, MA 02478 USAHarvard Univ, McLean Hosp, Sch Med, Alcohol & Drug Abuse Res Ctr, Belmont, MA 02478 USA
Mello, NK
;
Negus, SS
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, McLean Hosp, Sch Med, Alcohol & Drug Abuse Res Ctr, Belmont, MA 02478 USAHarvard Univ, McLean Hosp, Sch Med, Alcohol & Drug Abuse Res Ctr, Belmont, MA 02478 USA
机构:Rosalind Franklin Univ Med & Sci, Chicago Med Sch, Dept Physiol & Biophys, N Chicago, IL 60064 USA
Chen, Jun
;
Kang, Dawon
论文数: 0引用数: 0
h-index: 0
机构:
Rosalind Franklin Univ Med & Sci, Chicago Med Sch, Dept Physiol & Biophys, N Chicago, IL 60064 USA
Gyeongsang Natl Univ, Sch Med, Inst Hlth Sci, Med Res Ctr Neural Dysfunct,Dept Physiol, Jinju 660751, South KoreaRosalind Franklin Univ Med & Sci, Chicago Med Sch, Dept Physiol & Biophys, N Chicago, IL 60064 USA
Kang, Dawon
;
Xu, Jing
论文数: 0引用数: 0
h-index: 0
机构:
AbbVie Inc, Res & Dev, Global Prot Sci, N Chicago, IL 60064 USARosalind Franklin Univ Med & Sci, Chicago Med Sch, Dept Physiol & Biophys, N Chicago, IL 60064 USA
Xu, Jing
;
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Lake, Marc
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Hogan, James O.
论文数: 0引用数: 0
h-index: 0
机构:
Rosalind Franklin Univ Med & Sci, Chicago Med Sch, Dept Physiol & Biophys, N Chicago, IL 60064 USARosalind Franklin Univ Med & Sci, Chicago Med Sch, Dept Physiol & Biophys, N Chicago, IL 60064 USA
Hogan, James O.
;
Sun, Chaohong
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h-index: 0
机构:
AbbVie Inc, Res & Dev, Global Prot Sci, N Chicago, IL 60064 USARosalind Franklin Univ Med & Sci, Chicago Med Sch, Dept Physiol & Biophys, N Chicago, IL 60064 USA
Sun, Chaohong
;
Walter, Karl
论文数: 0引用数: 0
h-index: 0
机构:
AbbVie Inc, Res & Dev, Global Prot Sci, N Chicago, IL 60064 USARosalind Franklin Univ Med & Sci, Chicago Med Sch, Dept Physiol & Biophys, N Chicago, IL 60064 USA
Walter, Karl
;
Yao, Betty
论文数: 0引用数: 0
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机构:Rosalind Franklin Univ Med & Sci, Chicago Med Sch, Dept Physiol & Biophys, N Chicago, IL 60064 USA
Yao, Betty
;
Kim, Donghee
论文数: 0引用数: 0
h-index: 0
机构:
Rosalind Franklin Univ Med & Sci, Chicago Med Sch, Dept Physiol & Biophys, N Chicago, IL 60064 USARosalind Franklin Univ Med & Sci, Chicago Med Sch, Dept Physiol & Biophys, N Chicago, IL 60064 USA
机构:
Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Sch Med, Richmond, VA USA
Inst Anim Care & Use Comm, Memphis, TN USAVirginia Commonwealth Univ, Dept Pharmacol & Toxicol, Sch Med, Richmond, VA USA
Banks, Matthew L.
;
Czoty, Paul W.
论文数: 0引用数: 0
h-index: 0
机构:
Inst Anim Care & Use Comm, Memphis, TN USA
Wake Forest Sch Med, Dept Physiol & Pharmacol, Winston Salem, NC USAVirginia Commonwealth Univ, Dept Pharmacol & Toxicol, Sch Med, Richmond, VA USA
Czoty, Paul W.
;
Negus, Sidney S.
论文数: 0引用数: 0
h-index: 0
机构:
Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Sch Med, Richmond, VA USA
Inst Anim Care & Use Comm, Memphis, TN USAVirginia Commonwealth Univ, Dept Pharmacol & Toxicol, Sch Med, Richmond, VA USA
机构:
Harvard Univ, McLean Hosp, Sch Med, Alcohol & Drug Abuse Res Ctr, Belmont, MA 02478 USAHarvard Univ, McLean Hosp, Sch Med, Alcohol & Drug Abuse Res Ctr, Belmont, MA 02478 USA
Bowen, CA
;
Fischer, BD
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, McLean Hosp, Sch Med, Alcohol & Drug Abuse Res Ctr, Belmont, MA 02478 USAHarvard Univ, McLean Hosp, Sch Med, Alcohol & Drug Abuse Res Ctr, Belmont, MA 02478 USA
Fischer, BD
;
Mello, NK
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, McLean Hosp, Sch Med, Alcohol & Drug Abuse Res Ctr, Belmont, MA 02478 USAHarvard Univ, McLean Hosp, Sch Med, Alcohol & Drug Abuse Res Ctr, Belmont, MA 02478 USA
Mello, NK
;
Negus, SS
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, McLean Hosp, Sch Med, Alcohol & Drug Abuse Res Ctr, Belmont, MA 02478 USAHarvard Univ, McLean Hosp, Sch Med, Alcohol & Drug Abuse Res Ctr, Belmont, MA 02478 USA
机构:Rosalind Franklin Univ Med & Sci, Chicago Med Sch, Dept Physiol & Biophys, N Chicago, IL 60064 USA
Chen, Jun
;
Kang, Dawon
论文数: 0引用数: 0
h-index: 0
机构:
Rosalind Franklin Univ Med & Sci, Chicago Med Sch, Dept Physiol & Biophys, N Chicago, IL 60064 USA
Gyeongsang Natl Univ, Sch Med, Inst Hlth Sci, Med Res Ctr Neural Dysfunct,Dept Physiol, Jinju 660751, South KoreaRosalind Franklin Univ Med & Sci, Chicago Med Sch, Dept Physiol & Biophys, N Chicago, IL 60064 USA
Kang, Dawon
;
Xu, Jing
论文数: 0引用数: 0
h-index: 0
机构:
AbbVie Inc, Res & Dev, Global Prot Sci, N Chicago, IL 60064 USARosalind Franklin Univ Med & Sci, Chicago Med Sch, Dept Physiol & Biophys, N Chicago, IL 60064 USA
Xu, Jing
;
论文数: 引用数:
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机构:
Lake, Marc
;
Hogan, James O.
论文数: 0引用数: 0
h-index: 0
机构:
Rosalind Franklin Univ Med & Sci, Chicago Med Sch, Dept Physiol & Biophys, N Chicago, IL 60064 USARosalind Franklin Univ Med & Sci, Chicago Med Sch, Dept Physiol & Biophys, N Chicago, IL 60064 USA
Hogan, James O.
;
Sun, Chaohong
论文数: 0引用数: 0
h-index: 0
机构:
AbbVie Inc, Res & Dev, Global Prot Sci, N Chicago, IL 60064 USARosalind Franklin Univ Med & Sci, Chicago Med Sch, Dept Physiol & Biophys, N Chicago, IL 60064 USA
Sun, Chaohong
;
Walter, Karl
论文数: 0引用数: 0
h-index: 0
机构:
AbbVie Inc, Res & Dev, Global Prot Sci, N Chicago, IL 60064 USARosalind Franklin Univ Med & Sci, Chicago Med Sch, Dept Physiol & Biophys, N Chicago, IL 60064 USA
Walter, Karl
;
Yao, Betty
论文数: 0引用数: 0
h-index: 0
机构:Rosalind Franklin Univ Med & Sci, Chicago Med Sch, Dept Physiol & Biophys, N Chicago, IL 60064 USA
Yao, Betty
;
Kim, Donghee
论文数: 0引用数: 0
h-index: 0
机构:
Rosalind Franklin Univ Med & Sci, Chicago Med Sch, Dept Physiol & Biophys, N Chicago, IL 60064 USARosalind Franklin Univ Med & Sci, Chicago Med Sch, Dept Physiol & Biophys, N Chicago, IL 60064 USA