RESEARCH MONOGRAPH · KDC-MN-352
Naloxone
Naloxone, sold as Narcan, is the standard reversal agent for opioid overdose. It competitively binds and displaces opioids from the mu-opioid receptor with high affinity, restoring breathing within minutes when administered intramuscularly or as an intranasal spray. Public health programs have made intranasal naloxone available without prescription in pharmacies and from harm-reduction organizations across most of the US, and bystander administration is credited with thousands of overdose reversals annually. The short half-life means re-dosing may be required for long-acting opioids like methadone or fentanyl analogs. Not stocked by Kodiac. This monograph is provided for research and educational reference.
Intrigue 0–100 blends mechanism novelty, evidence strength, and translational potential. Kodiac editorial, not peer-reviewed.
Mu-opioid antagonist (short-acting)
A short-acting mu-opioid antagonist; the standard reversal agent for opioid overdose.
Abstract
Naloxone ((5alpha)-4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)morphinan-6-one; CAS 465-65-6; molecular formula C19H21NO4; molecular weight 327.37) is a short-acting mu-opioid antagonist approved by the FDA in 1971 (Narcan). The compound is a competitive antagonist at mu, kappa, and delta opioid receptors with preferential mu affinity (Ki approximately 1 nM). Unlike naltrexone, oral bioavailability is poor (less than 5 percent), restricting use to parenteral or intranasal administration. Plasma half-life is approximately 1 to 2 hours, shorter than most opioid agonists, requiring multiple doses or infusion in opioid overdose reversal where the half-life of the offending opioid exceeds naloxone's. The intranasal formulation (Narcan nasal spray, 4 mg) is widely available and has driven the modern public health response to the opioid overdose epidemic. Approved indications: opioid overdose reversal, postoperative opioid reversal, opioid-induced constipation (IV form alvimopan, methylnaltrexone for that latter). Used as the canonical mu-opioid antagonist in research.
Mechanism of action
Competitive mu-opioid receptor antagonist (Ki ~1 nM); reversal of opioid overdose. Short half-life requires repeated dosing for long-acting opioids.
Reported research dose ranges
Clinical IV 0.4 to 2 mg every 2 to 3 minutes as needed; intranasal 4 mg one nostril, repeat every 2 to 3 minutes.
References
- Boyer EW. Management of opioid analgesic overdose. N Engl J Med 2012.
- Doe-Simkins M, et al. Saved by the nose: bystander-administered intranasal naloxone hydrochloride for opioid overdose. Am J Public Health 2009.
- Faul M, et al. Disparity in naloxone administration by emergency medical service providers. Am J Public Health 2015.
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The full reference document is available as a research-use-only PDF download. Note: PDFs for newly added compounds may take a few hours to propagate after this article was published.
The full reference document is provided strictly for research use only. It reports research dose ranges from the published literature, not instructions for use in humans or animals.
FOR RESEARCH USE ONLY. Not for medical, diagnostic, or therapeutic purposes. Not for human consumption. All information is provided for research and educational purposes only.