Naloxone

Naloxone
source
IUPAC name	4,5α-epoxy-3,14-dihydroxy-17-(2-propen-1-yl)morphinan-6-one
Tradename	Narcan, Evzio, others
Drugs.com	monograph, naloxone
Routes of administration	Intravenous, intramuscular, subcutaneous, intranasal
Bioavailability	2% (oral), 30–40% (intranasal)
Protein bound	45%
Metabolism	Liver (extensive glucuronidation)
Elimination half-life	1–1.5 hours
Excretion	Urine
CAS number	465-65-6
PubChem	5284596
ChemSpiderID	4447648
UNII	36B82AMQ7N
ChEBI	7459
ChEMBL	337
ATC prefix	V03
ATC suffix	AB15

Naloxone. It is a life-saving medication used as an antidote to reverse opioid overdose, including overdoses from heroin, fentanyl, and prescription opioid medications. The drug works by competitively binding to mu-opioid receptors in the central nervous system, rapidly displacing other opioids and restoring normal respiration. Its development at the University of California and subsequent approval by the U.S. Food and Drug Administration has made it a cornerstone of public health responses to the opioid epidemic.

Medical uses

The primary medical use is the emergency treatment of known or suspected opioid overdose, characterized by respiratory depression, unconsciousness, and pinpoint pupils. It is a critical component of emergency medical services protocols used by paramedics and is included in many community-based harm reduction programs. Administration is indicated for overdoses involving natural opiates like morphine and codeine, semi-synthetic opioids such as oxycodone and hydrocodone, and fully synthetic opioids including fentanyl and methadone. It is also used in clinical settings to reverse unintended opioid effects after surgery and to diagnose suspected opioid dependence. The World Health Organization includes it on its List of Essential Medicines.

Pharmacology

Naloxone functions as a competitive opioid antagonist with a particularly high affinity for the mu-opioid receptor, the primary site mediating the life-threatening effects of opioid overdose. Its molecular structure is a derivative of the oxymorphone molecule, modified to remove agonist activity. Upon administration, it binds to opioid receptors without activating them, displacing opioid molecules and reversing central nervous system and respiratory depression. It has negligible agonist activity at other opioid receptor types like the delta and kappa receptors. Metabolism occurs primarily in the liver via glucuronide conjugation, and the metabolites are excreted in the urine.

History

The compound was first synthesized in 1961 by chemist Jack Fishman and pharmacologist Mozes J. Lewenstein, while working at the Laboratories of Applied Biology in New York City. Its development followed research into opioid antagonists at the University of California, San Francisco and other institutions. The U.S. Food and Drug Administration approved naloxone for the treatment of opioid overdose in 1971. For decades, its use was largely confined to hospital emergency departments and ambulance services. A significant shift began in the 1990s and 2000s with pilot programs, such as those initiated by the Harm Reduction Coalition, to distribute it to people who use drugs and their communities, a practice now widespread across North America and Europe.

Society and culture

Naloxone access and distribution have become central elements in the public health response to the opioid crisis in countries like the United States, Canada, and the United Kingdom. Legislative efforts, often called Good Samaritan laws, have been enacted in many states and provinces to protect laypersons who administer it during an overdose emergency. Brand name products include the auto-injector Evzio and the intranasal spray Narcan, marketed by Emergent BioSolutions. Its availability without a prescription from pharmacies has expanded significantly, driven by advocacy from organizations like the National Institute on Drug Abuse and the American Medical Association.

Research

Ongoing research focuses on developing new formulations with longer duration of action to counteract the effects of long-acting opioids like methadone and extended-release oxycodone. Studies are investigating the potential of combining it with other agents, such as the nicotinic antagonist atipamezole, to provide broader overdose protection. Investigations into its efficacy against novel synthetic opioids like carfentanil and various fentanyl analogues are critical. Furthermore, clinical trials, some funded by the National Institutes of Health, are exploring its use in conditions beyond overdose, including for the treatment of septic shock and pruritus induced by intrathecal opioids.

Category:Opioid antagonists Category:World Health Organization essential medicines Category:Emergency medications