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Journal article
Nalbuphine Potentiates Reversal of Fentanyl Overdose by Naloxone
Pharmaceuticals (Basel, Switzerland), v 17(7), 866
02 Jul 2024
PMID: 39065717
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Developing an effective antidote for fentanyl-induced overdose to achieve timely reversal is an unmet public health need. Previously, we found that naloxone derivative NX90 with mild kappa-opioid agonistic properties was three-fold more effective than the parent naloxone in reversing a fentanyl overdose in rats. To investigate whether kappa-agonistic properties could indeed augment the robustness of overdose reversal, we evaluated a kappa-agonist/mu -antagonist nalbuphine (NB) as well as its combinations with naloxone (NX) in a fentanyl overdose model in rodents. An administration of either NB or NX as single agents at 0.1 mg/kg doses produced a full recovery in 90 +/- 9.9 min and 11.4 +/- 2.7 min, respectively. A higher dose of NX at 0.2 mg/kg reversed an overdose within 4.8 +/- 1.0 min. In contrast to that, the coadministration of NB and NX at 0.1 mg/kg each produced a synergistic effect, with overdose reversal in 3.4 +/- 0.2 min. The coadministration of NX and NB at sub-therapeutic doses of 0.05 mg/kg each was also 1.2-fold more effective than NX at 0.2 mg/kg. We further found that co-administration of NB at different doses (0.025, 0.05, 0.1 mg/kg) and ratios (1:4 and 1:1) with NX had differential effects on overdose reversal, cardiorespiratory liabilities, and analgesia.
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Details
- Title
- Nalbuphine Potentiates Reversal of Fentanyl Overdose by Naloxone
- Creators
- Mihai Cernea - Univ Agr Sci & Vet Med, Fac Vet Med, Dept Pharmacol, Cluj Napoca 400372, RomaniaGeorgiy Nikonov - Kappa Pharmaceut LLC, Alachua, FL 32615 USAJanna Ataiants - Drexel University, Community Health and PreventionCristina Stefanut - Univ Agr Sci & Vet Med, Fac Vet Med, Dept Pharmacol, Cluj Napoca 400372, RomaniaJohn Abernethy - Serodopa Therapeut Inc, Gainesville, FL 32601 USAMichael Voronkov - Kappa Pharmaceut LLC, Alachua, FL 32615 USA
- Publication Details
- Pharmaceuticals (Basel, Switzerland), v 17(7), 866
- Publisher
- Mdpi
- Number of pages
- 9
- Grant note
- Serodopa Therapeutics, Inc. Kappa Pharmaceuticals, LLC
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Community Health and Prevention
- Web of Science ID
- WOS:001277638100001
- Scopus ID
- 2-s2.0-85199859452
- Other Identifier
- 991022005884504721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Chemistry, Medicinal
- Pharmacology & Pharmacy