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<p>Medications for opioid use disorder (OUD) and overdose have been available for decades, yet nearly 70% of fatal drug overdoses in the United States are attributed to the opioid receptor agonist fentanyl and its analogs. There is a pressing need for more and better medications that reduce fentanyl use and prevent overdose. A humanized (h) monoclonal antibody (mAb) targeting fentanyl, hHY6-F9, was tested for attenuating intravenous fentanyl self-administration and reversing and preventing fentanyl-induced ventilatory depression in rhesus monkeys. A single administration of hHY6-F9 significantly decreased fentanyl, but not heroin or cocaine, self-administration. In some monkeys, fentanyl self-administration remained decreased for ~ 2 weeks. hHY6-F9 was as effective as 32&#xa0;µg/kg naloxone in reversing fentanyl-induced ventilatory depression, with a single administration protecting against fentanyl-induced ventilatory depression for 2–3 weeks. Moreover, pharmacokinetic analyses indicate that hHY6-F9 continued to sequester fentanyl in the serum for 2 weeks. This study demonstrates that hHY6-F9 selectively attenuates the positive reinforcing and ventilatory depressant effects of fentanyl, indicating its possible utility for preventing relapse and overdose.</p>

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A humanized monoclonal antibody attenuates fentanyl self-administration and reverses and prevents fentanyl-induced ventilatory depression in rhesus monkeys

  • 期刊论文

  • 发表日期：

    2025年2月5日

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  • Lindsey K. Galbo-Thomma,
  • Courtney Marecki,
  • Caroline M. Kim,
  • Takato Hiranita,
  • Julia R. Taylor,
  • David R. Maguire,
  • Dustin Hicks,
  • Ann Gebo,
  • Aaron Khaimraj,
  • Carly Baehr,
  • Marco Pravetoni,
  • Charles P. France

摘要

Medications for opioid use disorder (OUD) and overdose have been available for decades, yet nearly 70% of fatal drug overdoses in the United States are attributed to the opioid receptor agonist fentanyl and its analogs. There is a pressing need for more and better medications that reduce fentanyl use and prevent overdose. A humanized (h) monoclonal antibody (mAb) targeting fentanyl, hHY6-F9, was tested for attenuating intravenous fentanyl self-administration and reversing and preventing fentanyl-induced ventilatory depression in rhesus monkeys. A single administration of hHY6-F9 significantly decreased fentanyl, but not heroin or cocaine, self-administration. In some monkeys, fentanyl self-administration remained decreased for ~ 2 weeks. hHY6-F9 was as effective as 32 µg/kg naloxone in reversing fentanyl-induced ventilatory depression, with a single administration protecting against fentanyl-induced ventilatory depression for 2–3 weeks. Moreover, pharmacokinetic analyses indicate that hHY6-F9 continued to sequester fentanyl in the serum for 2 weeks. This study demonstrates that hHY6-F9 selectively attenuates the positive reinforcing and ventilatory depressant effects of fentanyl, indicating its possible utility for preventing relapse and overdose.