Naloxone
Encyclopedia
Naloxone is an opioid
antagonist drug developed by Sankyo in the 1960s. Naloxone is a drug
used to counter the effects of opiate
overdose
, for example heroin or morphine
overdose. Naloxone is specifically used to counteract life-threatening depression of the central nervous system and respiratory system. Naloxone is also experimentally used in the treatment for congenital insensitivity to pain with anhidrosis
(CIPA), an extremely rare disorder (1 in 125 million) that renders one unable to feel pain. It is marketed under various trademarks including Narcan, Nalone, and Narcanti, and has sometimes been mistakenly called "naltrexate." It is not to be confused with naltrexone
, an opioid receptor
antagonist
with qualitatively different effects, used for dependence treatment rather than emergency overdose treatment.
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
.
from thebaine
. The chemical structure
of naloxone resembles that of oxymorphone
, the only difference being the substitution of the N
-methyl group
with an allyl
(prop-2-enyl) group. The name naloxone has been derived from N-allyl and oxymorphone.
, Philadelphia, New York State, Baltimore
, Boston
, Los Angeles
, Milwaukee, and Chicago
, with pilot projects started in Scotland
in 2006 . Also in the UK, in December 2008 the Welsh Assembly Government announced intention to establish demonstration sites for ‘take home’ 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is being increasingly superseded by naltrexone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 esophagitis
associated with opioid therapy in mechanically-ventilated acute care patients.
The combination oxycodone/naloxone
is used for the prophylaxis of opioid-induced constipation in patients requiring strong opioid therapy under the trade name Targin and in the Netherlands
under Targinact.
-addicted patients detox
. Suboxone contains four parts buprenorphine
and one part naloxone, while Subutex contains only buprenorphrine. Naloxone was added to Suboxone in an effort to dissuade patients from grinding it up for abuse in combination with opiates. Intravenously administered naloxone is supposed to block the effects of any opiates and cause the user to go into immediate withdrawal, however it does not do that if you have a tolerance for suboxone and always start at a low dose. Oral or sublingual
administration affects only the gastrointestinal tract
, and has the added benefit of helping to reverse constipation
and lowered bowel motility caused by chronic medical use, or abuse, of a variety of opioids. Because of possible side effects of naloxone in some patients, chemical detox is often begun with Suboxone's sister drug, Subutex, which does not contain naloxone.
. According to the study: "In three of 14 patients, depersonalization
symptoms disappeared entirely and seven patients showed a marked improvement. The therapeutic effect of naloxone provides evidence for the role of the endogenous opioid system in the pathogenesis of depersonalization."
Naloxone has been shown to block the action of pain-lowering endorphin
s which the body produces naturally. The likely reason for this is that these endorphins operate on the same opioid receptors that Naloxone blocks. Naloxone is capable of blocking a placebo
pain-lowering response, both in clinical and experimental pain, if the placebo is administered together with a hidden or blind injection of naloxone. Other studies have found that placebo alone can activate the body's μ-opioid endorphin system, delivering pain relief via the same receptor mechanism as morphine.
for naloxone has expired. It is available in generic
forms.
salt
has CAS 357-08-4 and the hydrochloride salt with 2 molecules of water, hydrochloride dihydrate, has CAS 51481-60-8.
Opioid
An opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...
antagonist drug developed by Sankyo in the 1960s. Naloxone is a drug
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
used to counter the effects of opiate
Opiate
In medicine, the term opiate describes any of the narcotic opioid alkaloids found as natural products in the opium poppy plant.-Overview:Opiates are so named because they are constituents or derivatives of constituents found in opium, which is processed from the latex sap of the opium poppy,...
overdose
Drug overdose
The term drug overdose describes the ingestion or application of a drug or other substance in quantities greater than are recommended or generally practiced...
, for example heroin or morphine
Morphine
Morphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...
overdose. Naloxone is specifically used to counteract life-threatening depression of the central nervous system and respiratory system. Naloxone is also experimentally used in the treatment for congenital insensitivity to pain with anhidrosis
Congenital insensitivity to pain with anhidrosis
Congenital insensitivity to pain with anhidrosis is an extremely rare inherited disorder of the nervous system which prevents the sensation of pain, heat, cold, or any real nerve-related sensations ; however, patients can still feel pressure. CIPA is the fourth type of hereditary sensory and...
(CIPA), an extremely rare disorder (1 in 125 million) that renders one unable to feel pain. It is marketed under various trademarks including Narcan, Nalone, and Narcanti, and has sometimes been mistakenly called "naltrexate." It is not to be confused with naltrexone
Naltrexone
Naltrexone is an opioid receptor antagonist used primarily in the management of alcohol dependence and opioid dependence. It is marketed in generic form as its hydrochloride salt, naltrexone hydrochloride, and marketed under the trade names Revia and Depade...
, an opioid receptor
Opioid receptor
Opioid receptors are a group of G protein-coupled receptors with opioids as ligands. The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins and nociceptin. The opioid receptors are ~40% identical to somatostatin receptors...
antagonist
Receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
with qualitatively different effects, used for dependence treatment rather than emergency overdose treatment.
Pharmacodynamics
Naloxone has an extremely high affinity for μ-opioid receptorsMu Opioid receptor
The μ-opioid receptors are a class of opioid receptors with high affinity for enkephalins and beta-endorphin but low affinity for dynorphins. They are also referred to as μ opioid peptide receptors. The prototypical μ receptor agonist is the opium alkaloid morphine; μ refers to morphine...
in the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
. Naloxone is a μ-opioid receptor competitive antagonist
Competitive antagonist
A competitive antagonist is a receptor antagonist that binds to a receptor but does not activate the receptor. The antagonist will compete with available agonist for receptor binding sites on the same receptor...
, and its rapid blockade of those receptors often produces rapid onset of withdrawal
Withdrawal
Withdrawal can refer to any sort of separation, but is most commonly used to describe the group of symptoms that occurs upon the abrupt discontinuation/separation or a decrease in dosage of the intake of medications, recreational drugs, and alcohol...
symptoms. Naloxone also has an antagonist action, though with a lower affinity, at κ-
Kappa Opioid receptor
The κ-opioid receptor is a protein that in humans is encoded by the OPRK1 gene. The κ-opioid receptor is one of five related receptors that bind opium-like compounds in the brain and are responsible for mediating the effects of these compounds...
and δ-opioid receptors
Delta Opioid receptor
The δ-opioid receptors, also known as delta opioid receptor or simply delta receptor, abbreviated DOR, is an opioid receptor that has enkephalins as its endogenous ligands.-Function:...
.
Chemistry
Naloxone is synthesizedChemical synthesis
In chemistry, chemical synthesis is purposeful execution of chemical reactions to get a product, or several products. This happens by physical and chemical manipulations usually involving one or more reactions...
from thebaine
Thebaine
Thebaine , its name coming from the Greek Θῆβαι, Thēbai, an ancient city in Upper Egypt, is an opiate alkaloid. A minor constituent of opium, thebaine is chemically similar to both morphine and codeine, but has stimulatory rather than depressant effects, causing convulsions similar to strychnine...
. The chemical structure
Chemical structure
A chemical structure includes molecular geometry, electronic structure and crystal structure of molecules. Molecular geometry refers to the spatial arrangement of atoms in a molecule and the chemical bonds that hold the atoms together. Molecular geometry can range from the very simple, such as...
of naloxone resembles that of oxymorphone
Oxymorphone
Oxymorphone or 14-Hydroxydihydromorphinone is a powerful semi-synthetic opioid analgesic first developed in Germany circa 1914, patented in the USA by Endo Pharmaceuticals in 1955 and introduced to the United States market in January 1959 and other countries around the same time...
, the only difference being the substitution of the N
Amine
Amines are organic compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group. Important amines include amino acids, biogenic amines,...
-methyl group
Functional group
In organic chemistry, functional groups are specific groups of atoms within molecules that are responsible for the characteristic chemical reactions of those molecules. The same functional group will undergo the same or similar chemical reaction regardless of the size of the molecule it is a part of...
with an allyl
Allyl
An allyl group is a substituent with the structural formula H2C=CH-CH2R, where R is the connection to the rest of the molecule. It is made up of a methylene , attached to a vinyl group . The name is derived from the Latin word for garlic, Allium sativum. Theodor Wertheim isolated an allyl...
(prop-2-enyl) group. The name naloxone has been derived from N-allyl and oxymorphone.
Administration
Naloxone is most commonly injected intravenously for fastest action. The drug generally acts within a minute, and its effects may last up to 45 minutes. It can also be administered via intramuscular or subcutaneous injection. Use of a wedge device (nasal atomizer) attached to a syringe to create a mist delivering the drug to the nasal mucosa may also be utilized, although this solution is more likely utilized outside of a clinical facility.Counteracting opiate overdose and addiction
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 under way in San Francisco, New MexicoNew Mexico
New Mexico is a state located in the southwest and western regions of the United States. New Mexico is also usually considered one of the Mountain States. With a population density of 16 per square mile, New Mexico is the sixth-most sparsely inhabited U.S...
, Philadelphia, New York State, Baltimore
Baltimore
Baltimore is the largest independent city in the United States and the largest city and cultural center of the US state of Maryland. The city is located in central Maryland along the tidal portion of the Patapsco River, an arm of the Chesapeake Bay. Baltimore is sometimes referred to as Baltimore...
, Boston
Boston
Boston is the capital of and largest city in Massachusetts, and is one of the oldest cities in the United States. The largest city in New England, Boston is regarded as the unofficial "Capital of New England" for its economic and cultural impact on the entire New England region. The city proper had...
, Los Angeles
Los Ángeles
Los Ángeles is the capital of the province of Biobío, in the commune of the same name, in Region VIII , in the center-south of Chile. It is located between the Laja and Biobío rivers. The population is 123,445 inhabitants...
, Milwaukee, and Chicago
Chicago
Chicago is the largest city in the US state of Illinois. With nearly 2.7 million residents, it is the most populous city in the Midwestern United States and the third most populous in the US, after New York City and Los Angeles...
, with pilot projects started in Scotland
Scotland
Scotland is a country that is part of the United Kingdom. Occupying the northern third of the island of Great Britain, it shares a border with England to the south and is bounded by the North Sea to the east, the Atlantic Ocean to the north and west, and the North Channel and Irish Sea to the...
in 2006 . Also in the UK, in December 2008 the Welsh Assembly Government announced intention to establish demonstration sites for ‘take home’ Naloxone. While naloxone is still often used in emergency treatments for opioid overdose, its clinical use in the long-term treatment of opioid addiction
Substance dependence
The section about substance dependence in the Diagnostic and Statistical Manual of Mental Disorders does not use the word addiction at all. It explains:...
is being increasingly superseded by naltrexone
Naltrexone
Naltrexone is an opioid receptor antagonist used primarily in the management of alcohol dependence and opioid dependence. It is marketed in generic form as its hydrochloride salt, naltrexone hydrochloride, and marketed under the trade names Revia and Depade...
. 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
Enteral
In pharmacology, Enteral is a term used to describe routes of drug administration that involve absorption of the drug through the gastrointestinal tract. The term may also be used to describe something as residing in the gastrointestinal tract...
naloxone has been successfully used in the reduction of gastritis
Gastritis
Gastritis is an inflammation of the lining of the stomach, and has many possible causes. The main acute causes are excessive alcohol consumption or prolonged use of nonsteroidal anti-inflammatory drugs such as aspirin or ibuprofen. Sometimes gastritis develops after major surgery, traumatic...
and esophagitis
Esophagitis
Esophagitis is inflammation of the esophagus. It may be acute or chronic. The acute esophagitis can be catarrhal or phlegmonous, whereas the chronic esophagitis may be hypertrophic or atrophic.-Infectious:...
associated with opioid therapy in mechanically-ventilated acute care patients.
The combination oxycodone/naloxone
Oxycodone/naloxone
The combination oxycodone/naloxone is an opioid analgesic available as managed-release tablets under the trade names Targin , Targiniq and Targinact. Oxycodone is responsible for the pain-relieving effects, while naloxone reduces opioid-induced constipation. Constipation was significantly improved...
is used for the prophylaxis of opioid-induced constipation in patients requiring strong opioid therapy under the trade name Targin and in the Netherlands
Netherlands
The Netherlands is a constituent country of the Kingdom of the Netherlands, located mainly in North-West Europe and with several islands in the Caribbean. Mainland Netherlands borders the North Sea to the north and west, Belgium to the south, and Germany to the east, and shares maritime borders...
under Targinact.
Preventing opioid abuse
Naloxone is used as a secondary chemical in the drug Suboxone. Suboxone and Subutex were created to help opiateOpiate
In medicine, the term opiate describes any of the narcotic opioid alkaloids found as natural products in the opium poppy plant.-Overview:Opiates are so named because they are constituents or derivatives of constituents found in opium, which is processed from the latex sap of the opium poppy,...
-addicted patients detox
Detox
Detoxification is the physiological or medicinal removal of toxic substances from a living organism, including, but not limited to, the human body and additionally can refer to the period of withdrawal during which an organism returns to homeostasis after long-term use of an addictive substance...
. Suboxone contains four parts buprenorphine
Buprenorphine
Buprenorphine is a semi-synthetic opioid that is used...
and one part naloxone, while Subutex contains only buprenorphrine. Naloxone was added to Suboxone in an effort to dissuade patients from grinding it up for abuse in combination with opiates. Intravenously administered naloxone is supposed to block the effects of any opiates and cause the user to go into immediate withdrawal, however it does not do that if you have a tolerance for suboxone and always start at a low dose. Oral or sublingual
Sublingual
Sublingual, literally 'under the tongue', from Latin, refers to the pharmacological route of administration by which drugs diffuse into the blood through tissues under the tongue...
administration affects only the gastrointestinal tract
Gastrointestinal tract
The human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....
, and has the added benefit of helping to reverse constipation
Constipation
Constipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation...
and lowered bowel motility caused by chronic medical use, or abuse, of a variety of opioids. Because of possible side effects of naloxone in some patients, chemical detox is often begun with Suboxone's sister drug, Subutex, which does not contain naloxone.
Depersonalization disorder
A 2001 Russian study has shown that naloxone can be used to treat depersonalization disorderDepersonalization disorder
Depersonalization disorder is a dissociative disorder in which the sufferer is affected by persistent or recurrent feelings of depersonalization and/or derealization. Diagnostic criteria include persistent or recurrent experiences of feeling detached from one's mental processes or body...
. According to the study: "In three of 14 patients, depersonalization
Depersonalization
Depersonalization is an anomaly of the mechanism by which an individual has self-awareness. It is a feeling of watching oneself act, while having no control over a situation. Sufferers feel they have changed, and the world has become less real, vague, dreamlike, or lacking in significance...
symptoms disappeared entirely and seven patients showed a marked improvement. The therapeutic effect of naloxone provides evidence for the role of the endogenous opioid system in the pathogenesis of depersonalization."
Side-effects
Possible side effects include: change in mood, increased sweating, nausea, nervousness, restlessness, trembling, vomiting, allergic reactions such as rash or swelling, dizziness, fainting, fast or irregular pulse, flushing, headache, heart rhythm changes, seizures, sudden chest pain.Naloxone has been shown to block the action of pain-lowering endorphin
Endorphin
Endorphins are endogenous opioid peptides that function as neurotransmitters. They are produced by the pituitary gland and the hypothalamus in vertebrates during exercise, excitement, pain, consumption of spicy food, love and orgasm, and they resemble the opiates in their abilities to produce...
s which the body produces naturally. The likely reason for this is that these endorphins operate on the same opioid receptors that Naloxone blocks. Naloxone is capable of blocking a placebo
Placebo
A placebo is a simulated or otherwise medically ineffectual treatment for a disease or other medical condition intended to deceive the recipient...
pain-lowering response, both in clinical and experimental pain, if the placebo is administered together with a hidden or blind injection of naloxone. Other studies have found that placebo alone can activate the body's μ-opioid endorphin system, delivering pain relief via the same receptor mechanism as morphine.
Legal status
The patentPatent
A patent is a form of intellectual property. It consists of a set of exclusive rights granted by a sovereign state to an inventor or their assignee for a limited period of time in exchange for the public disclosure of an invention....
for naloxone has expired. It is available in generic
Generic drug
A generic drug is a drug defined as "a drug product that is comparable to brand/reference listed drug product in dosage form, strength, route of administration, quality and performance characteristics, and intended use." It has also been defined as a term referring to any drug marketed under its...
forms.
Identification
The CAS number of naloxone is 465-65-6; the anhydrous hydrochlorideHydrochloride
In chemistry, hydrochlorides are salts resulting, or regarded as resulting, from the reaction of hydrochloric acid with an organic base . This is also known as muriate, derived from hydrochloric acid's other name: muriatic acid....
salt
Salt
In chemistry, salts are ionic compounds that result from the neutralization reaction of an acid and a base. They are composed of cations and anions so that the product is electrically neutral...
has CAS 357-08-4 and the hydrochloride salt with 2 molecules of water, hydrochloride dihydrate, has CAS 51481-60-8.
External links
- Chicago Recovery Alliance's naloxone distribution project
- Report on Naloxone and other opiate antidotes, by the International Programme on Chemical Safety