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OtherDrug Discovery and Translational Medicine

Monoclonal antibodies counteract opioid-induced behavioral and toxic effects in mice and rats

Carly Anne Baehr, April Huseby Kelcher, Aaron Khaimraj, Dana E Reed, Sujata G Pandit, David AuCoin, Saadyah Averick and Marco Pravetoni
Journal of Pharmacology and Experimental Therapeutics September 26, 2020, JPET-AR-2020-000124; DOI: https://doi.org/10.1124/jpet.120.000124
Carly Anne Baehr
1University of Minnesota, United States
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April Huseby Kelcher
2Pharmacology; Psychiatry and Behavioral Sciences, University of Minnesota, United States
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Aaron Khaimraj
3Pharmacology, University of Minnesota, United States
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Dana E Reed
4Microbiology and Immunology, University of Nevada Reno, United States
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Sujata G Pandit
4Microbiology and Immunology, University of Nevada Reno, United States
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David AuCoin
4Microbiology and Immunology, University of Nevada Reno, United States
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Saadyah Averick
5Allegheny Health Network, United States
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Marco Pravetoni
6Pharmacology, University of Minnesota Medical School, United States
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  • For correspondence: prave001@umn.edu
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Abstract

Monoclonal antibodies (mAb) and vaccines have been proposed as medical countermeasures to treat opioid use disorder (OUD) and prevent opioid overdose. In contrast to current pharmacotherapies (e.g., methadone, buprenorphine, naltrexone, and naloxone) for OUD and overdose, which target brain opioid receptors, mAb and vaccine-generated polyclonal antibodies sequester the target opioid in the serum and reduce drug distribution to the brain. Further, mAb offer several potential clinical benefits over approved medications, such as longer serum half-life, high selectivity, reduced side effects, and low abuse liability. Using magnetic enrichment to isolate opioid-specific B cell lymphocytes prior to fusion with myeloma partners, this study identified a series of murine hybridoma cell lines expressing mAb with high affinity for opioids of clinical interest, including oxycodone, heroin and its active metabolites, and fentanyl. In mice, passive immunization with lead mAb against oxycodone, heroin, and fentanyl reduced drug-induced antinociception and the distribution of the target opioid to the brain. In mice and rats, mAb pre-treatment reduced fentanyl-induced respiratory depression and bradycardia, two risk factors for opioid-related overdose fatality. Overall, these results support use of mAb to counteract toxic effects of opioids and other chemical threats.

Significance Statement The incidence of fatal overdoses due to the widespread access to heroin, prescription opioids, and fentanyl suggests that current FDA-approved countermeasures are not sufficient to mitigate the opioid epidemic. Monoclonal antibodies (mAb) may provide acute protection from overdose by binding to circulating opioids in serum. Use of mAb prophylactically, or post-exposure in combination with naloxone, may reduce hospitalization and increase survival.

  • addiction
  • antibodies
  • blood-brain barrier
  • monoclonal antibody
  • opioids
  • pharmacokinetics
  • substance abuse
  • Copyright © 2020 American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 384 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 384, Issue 2
1 Feb 2023
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OtherDrug Discovery and Translational Medicine

Development of mAb to counteract opioids

Carly Anne Baehr, April Huseby Kelcher, Aaron Khaimraj, Dana E Reed, Sujata G Pandit, David AuCoin, Saadyah Averick and Marco Pravetoni
Journal of Pharmacology and Experimental Therapeutics September 26, 2020, JPET-AR-2020-000124; DOI: https://doi.org/10.1124/jpet.120.000124

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OtherDrug Discovery and Translational Medicine

Development of mAb to counteract opioids

Carly Anne Baehr, April Huseby Kelcher, Aaron Khaimraj, Dana E Reed, Sujata G Pandit, David AuCoin, Saadyah Averick and Marco Pravetoni
Journal of Pharmacology and Experimental Therapeutics September 26, 2020, JPET-AR-2020-000124; DOI: https://doi.org/10.1124/jpet.120.000124
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