Article: Naloxone

Naloxone
Systematic (IUPAC) name
17-allyl-4,5α-epoxy- 3,14-dihydroxymorphinan-6-one
Identifiers
CAS number	465-65-6
ATC code	V03AB15
PubChem	4425
DrugBank	APRD00025
Chemical data
Formula	C19H21NO4
Mol. weight	327.27
Pharmacokinetic data
Bioavailability	2% (90% absorption but high first-pass metabolism)
Metabolism	Liver
Half life	1-1.5 hours
Excretion	Urine, Biliary
Therapeutic considerations
Pregnancy cat.	B (USA) B1 (Aus)
Legal status	Schedule 4 (Aus)
Routes	IV, IM

Naloxone is a drug used to counter the effects of opioid overdose, for example heroin and morphine overdose. Specifically, naloxone is used in opioid overdoses for countering life-threatening depression of the central nervous system and respiratory system. It is marketed under trade names including Narcan, Nalone, and Narcanti and has sometimes been mistakenly called "naltrexate."

The drug is derived from thebaine and has an extremely high affinity for μ-opioid receptors in the central nervous system. Naloxone is a μ-opioid receptor competitive antagonist, and its rapid blockade of those receptors often produces rapid onset of withdrawal symptoms. Naloxone also has an antagonist action, though with a lower affinity, at κ- and δ-opioid receptors. Structurally, Naloxone can be described as a substituted oxymorphone—here the tertiary amine methyl substituent is replaced with prop-2-enyl.

Naloxone is injected, usually initially intravenously for fastest action. The drug acts after about two minutes, and its effects may last about 45 minutes. Other routes, including intramuscular injection and intranasal injection (use of a wedge device attached to the syringe to create a mist delivering the drug to the nasal mucosa) may also be utilized, although these are more likely in the prehospital setting.

Naloxone has been distributed as part of emergency kits to heroin users, and this has been shown to reduce rates of fatal overdose. Projects of this type are underway in San Francisco and Chicago, and pilot projects started in Scotland in 2006.^[1]

The drug also blocks the action of pain-lowering endorphins which the body produces naturally. The likely reason for this is that these endorphins operate on the same opioid receptors. In one experiment, women treated with naloxone reported higher pain levels during childbirth than women not so treated; in another experiment, the pain lowering effect of placebos was blocked if the placebos were administered along with naloxone.

While naloxone is still often used in emergency treatments for opioid overdose, its clinical use in the long-term treatment of opioid addiction is being increasingly superseded by naltrexone. Naltrexone is structurally similar but has a slightly increased affinity for κ-opioid receptors over naloxone, can be administered orally and has a longer duration of action.

Enteral naloxone has been successfully used in the reduction of gastritis and oesophagitis associated with opioid therapy in mechanically-ventilated acute care patients.^[2]

The patent for Naloxone has expired and it is manufactured by various companies. The CAS number of naloxone is 465-65-6; the anhydrous hydrochloride salt has CAS 357-08-4 and the hydrochloride salt with 2 molecules of water has CAS 51481-60-8.