Carfentanil or carfentanyl, sold under the brand name Wildnil, is a very potent

opioid Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid use ...

analgesic An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...

which is used in

veterinary medicine Veterinary medicine is the branch of medicine that deals with the prevention, management, diagnosis, and treatment of disease, disorder, and injury in animals. Along with this, it deals with animal rearing, husbandry, breeding, research on nutri ...

anesthetize ''Fear of a Blank Planet'' is the ninth studio album by British progressive rock band Porcupine Tree and their best selling before 2009's '' The Incident''. It was released on 16 April 2007 in the UK and the rest of Europe by Roadrunner, 2 ...

large animals such as

elephant Elephants are the largest existing land animals. Three living species are currently recognised: the African bush elephant, the African forest elephant, and the Asian elephant. They are the only surviving members of the family Elephantida ...

s and

rhinoceros A rhinoceros (; ; ), commonly abbreviated to rhino, is a member of any of the five extant species (or numerous extinct species) of odd-toed ungulates in the family Rhinocerotidae. (It can also refer to a member of any of the extinct specie ...

es. It is typically administered in this context by tranquilizer dart. Carfentanil has also been used in humans for imaging of

opioid receptor Opioid receptors are a group of inhibitory 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 ...

s. It has additionally been used as a

recreational drug Recreational drug use indicates the use of one or more psychoactive drugs to induce an altered state of consciousness either for pleasure or for some other casual purpose or pastime by modifying the perceptions and emotions of the user. When a ...

, typically by injection, insufflation, or

inhalation Inhalation (or Inspiration) happens when air or other gases enter the lungs. Inhalation of air Inhalation of air, as part of the cycle of breathing, is a vital process for all human life. The process is autonomic (though there are exceptions ...

. Deaths have been reported in association with carfentanil. Effects and

side effect In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...

s of carfentanil in humans are similar to those of other opioids and include

euphoria Euphoria ( ) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music and d ...

, relaxation,

pain relief Pain management is an aspect of medicine and health care involving relief of pain (pain relief, analgesia, pain control) in various dimensions, from acute and simple to chronic and challenging. Most physicians and other health professional ...

, pupil constriction, drowsiness,

sedation Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure. Examples of drugs which can be used for sedation include isoflurane, diethyl ether, ...

, slowed heart rate, low blood pressure, lowered body temperature,

loss of consciousness Loss may refer to: Arts, entertainment, and media Music * ''Loss'' (Bass Communion album) (2006) * ''Loss'' (Mull Historical Society album) (2001) *"Loss", a song by God Is an Astronaut from their self-titled album (2008) * Losses "(Lil Tjay son ...

, and suppression of breathing. The effects of carfentanil, including

overdose A drug overdose (overdose or OD) is the ingestion or application of a drug or other substance in quantities much greater than are recommended.

, can be reversed by the opioid antagonists

naloxone Naloxone, sold under the brand names Narcan (4 mg) and Kloxxado (8 mg) among others, is a medication used to reverse or reduce the effects of opioids. It is commonly used to counter decreased breathing in opioid overdose. Effects begin withi ...

and

naltrexone Naltrexone, sold under the brand name Revia among others, is a medication primarily used to manage alcohol or opioid use disorder by reducing cravings and feelings of euphoria associated with substance use disorder. It has also been foun ...

, though higher or multiple doses than usual may be necessary compared to other opioids. Carfentanil is a structural analogue of the

synthetic Synthetic things are composed of multiple parts, often with the implication that they are artificial. In particular, 'synthetic' may refer to: Science * Synthetic chemical or compound, produced by the process of chemical synthesis * Synthetic ...

opioid analgesic

fentanyl Fentanyl, also spelled fentanil, is a very potent synthetic opioid used as a pain medication. Together with other drugs, fentanyl is used for anesthesia. It is also used illicitly as a recreational drug, sometimes mixed with heroin, cocain ...

. It acts as an ultrapotent and highly selective

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ag ...

of the

μ-opioid receptor The μ-opioid receptors (MOR) are a class of opioid receptors with a high affinity for enkephalins and beta-endorphin, but a low affinity for dynorphins. They are also referred to as μ(''mu'')-opioid peptide (MOP) receptors. The prototypical ...

. Carfentanil was first synthesized in 1974 by a team of chemists at

Janssen Pharmaceutica Janssen Pharmaceuticals is a pharmaceutical company headquartered in Beerse, Belgium, and wholly-owned by Johnson & Johnson. It was founded in 1953 by Paul Janssen. In 1961, Janssen Pharmaceuticals was purchased by New Jersey-based American ...

which included

Paul Janssen Paul Adriaan Jan, Baron Janssen (12 September 1926 - 11 November 2003) was a Belgian physician. He was the founder of Janssen Pharmaceutica, a pharmaceutical company with over 20,000 employees which is now a subsidiary of Johnson & Johnson. Ea ...

. It was introduced into veterinary medicine in 1986. Carfentanil is legally controlled in most jurisdictions.

Uses

Veterinary use

Chosen for its high

therapeutic index The therapeutic index (TI; also referred to as therapeutic ratio) is a quantitative measurement of the relative safety of a drug. It is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes ...

, carfentanil was first sold in 1986 under the brand name "Wildnil" for use in combination with an α₂-receptor agonist as a tranquilizing agent for large mammals like hippos, rhinos, and elephants. Commercial production of Wildnil ceased in 2003; the drug is now available only in compounded form.

Clinical use

Carfentanil has been used at doses of less than 7 μg as a

radiotracer A radioactive tracer, radiotracer, or radioactive label is a chemical compound in which one or more atoms have been replaced by a radionuclide so by virtue of its radioactive decay it can be used to explore the mechanism of chemical reactions by tr ...

for

positron emission tomography Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes, and in other physiological activities including blood flow, ...

imaging of the

in the brain in humans.

Pharmacology

Pharmacodynamics

Carfentanil acts as a highly selective

of the

. It showed affinity values (K_i) of 0.051 nM for the μ-opioid receptor, 4.7 nM for the

δ-opioid receptor The δ-opioid receptor, also known as delta opioid receptor or simply delta receptor, abbreviated DOR or DOP, is an inhibitory 7-transmembrane G-protein coupled receptor coupled to the G protein Gi/G0 and has enkephalins as its endogenous lig ...

, and 13 nM for the

κ-opioid receptor The κ-opioid receptor or kappa opioid receptor, abbreviated KOR or KOP, is a G protein-coupled receptor that in humans is encoded by the ''OPRK1'' gene. The KOR is coupled to the G protein Gi/G0 and is one of four related receptors that bind ...

in rat brain. Thus, carfentanil displayed 90- and 250-fold selectivity for the μ-opioid receptor over the δ-opioid receptor and the κ-opioid receptor, respectively. With human proteins, the affinities were 0.024 nM for the μ-opioid receptor, 3.3 nM for the δ-opioid receptor, and 43 nM for the κ-opioid receptor, demonstrating 140- and 1,800-fold selectivity for the μ-opioid receptor over the δ- and κ-opioid receptors, respectively. Carfentanil appears to have higher affinity for the μ₁-opioid receptor over the μ₂-opioid receptor. Carfentanil has approximately 10,000 times the

potency Potency may refer to: * Potency (pharmacology), a measure of the activity of a drug in a biological system * Virility * Cell potency, a measure of the differentiation potential of stem cells * In homeopathic dilutions, potency is a measure of how ...

morphine Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies ('' Papaver somniferum''). It is mainly used as a pain medication, and is also commonly used recreationally, or to make other illicit opioids. T ...

, 4,000 times the potency of

heroin Heroin, also known as diacetylmorphine and diamorphine among other names, is a potent opioid mainly used as a recreational drug for its euphoric effects. Medical grade diamorphine is used as a pure hydrochloride salt. Various white and bro ...

, and 20 to 100 times the potency of fentanyl in animal studies. The effects of carfentanil are reversed by μ-opioid receptor antagonists like

and

, though higher than normal doses of these agents may be necessary in humans due to the extremely high potency of carfentanil.

Pharmacokinetics

lipophilic Lipophilicity (from Greek λίπος "fat" and φίλος "friendly"), refers to the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Such non-polar solvents are themselves lipo ...

chemical that can easily cross the

blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable border of endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of the central nervous system where ne ...

, carfentanil has a very rapid onset of action and is longer acting than fentanyl. Its

elimination half-life Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the b ...

in humans was 42 to 51 minutes following an

intravenous bolus Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...

at an average dose of 1.34 μg (19 ng/kg). However, in a case study of recreational exposure, the half-lives of carfentanil and its

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, ...

norcarfentanil were estimated to be 5.7 hours and 11.8 hours, respectively.

Chemistry

Carfentanil is an analogue of

and is also known as (4-methoxycarbonyl)fentanyl. Related analogues of fentanyl include 4-phenylfentanyl, lofentanil (3-methylcarfentanyl), N-methylcarfentanil,

R-30490 R-30490 (also known as 4-methoxymethylfentanyl) is an opioid analgesic related to the highly potent animal tranquilizer carfentanil, and with only slightly lower potency. It was first synthesised by a team of chemists at Janssen Pharmaceutica led ...

(4-methoxymethylfentanyl), sufentanil, and thiafentanil.

History

Increase in illicit use

Over three hundred cases of overdose related to fentanyl and fentanyl analogues were reported between August and November 2016 in several of the United States, including

Ohio Ohio () is a U.S. state, state in the Midwestern United States, Midwestern region of the United States. Of the List of states and territories of the United States, fifty U.S. states, it is the List of U.S. states and territories by area, 34th-l ...

West Virginia West Virginia is a state in the Appalachian, Mid-Atlantic and Southeastern regions of the United States.The Census Bureau and the Association of American Geographers classify West Virginia as part of the Southern United States while the ...

Indiana Indiana () is a U.S. state in the Midwestern United States. It is the 38th-largest by area and the 17th-most populous of the 50 States. Its capital and largest city is Indianapolis. Indiana was admitted to the United States as the 19th ...

Kentucky Kentucky ( , ), officially the Commonwealth of Kentucky, is a state in the Southeastern region of the United States and one of the states of the Upper South. It borders Illinois, Indiana, and Ohio to the north; West Virginia and Virginia ...

and

Florida Florida is a state located in the Southeastern region of the United States. Florida is bordered to the west by the Gulf of Mexico, to the northwest by Alabama, to the north by Georgia, to the east by the Bahamas and Atlantic Ocean, and ...

. In 2017, a

Milwaukee Milwaukee ( ), officially the City of Milwaukee, is both the most populous and most densely populated city in the U.S. state of Wisconsin and the county seat of Milwaukee County. With a population of 577,222 at the 2020 census, Milwaukee i ...

Wisconsin Wisconsin () is a state in the upper Midwestern United States. Wisconsin is the 25th-largest state by total area and the 20th-most populous. It is bordered by Minnesota to the west, Iowa to the southwest, Illinois to the south, Lake M ...

, man died from a carfentanil overdose, likely taken unknowingly with another illegal drug such as

cocaine Cocaine (from , from , ultimately from Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly used recreationally for its euphoric effects. It is primarily obtained from the leaves of two Coca species native to South Am ...

. Carfentanil is most often taken with

or by users who believe they are taking heroin. Carfentanil is added to or sold as heroin because it is less expensive, easier to obtain, and easier to manufacture than heroin. Health professionals are concerned about the potential escalation of public health consequences of its recreational use.

Importation from China

Authorities in Latvia and Lithuania reported seizing carfentanil as an illicit drug in the early 2000s. Around 2016, the United States and Canada reported a dramatic increase in shipment of carfentanil and other strong

drugs to customers in North America from Chinese chemical supply firms. In June 2016, the

Royal Canadian Mounted Police The Royal Canadian Mounted Police (RCMP; french: Gendarmerie royale du Canada; french: GRC, label=none), commonly known in English as the Mounties (and colloquially in French as ) is the federal and national police service of Canada. As poli ...

seized one kilogram of carfentanil shipped from China in a box labeled "printer accessories". According to the Canada Border Services Agency, the shipment contained 50 million lethal doses of the drug, more than enough to annihilate the entire population of the country, in containers labeled as toner cartridges for

HP LaserJet LaserJet as a brand name identifies the line of laser printers marketed by the American computer company Hewlett-Packard (HP). The HP LaserJet was the first popular desktop laser printer. Canon supplies both mechanisms and cartridges for most HP ...

printers. Carfentanil was not a controlled substance in China until 1 March 2017, and until then was manufactured legally and sold openly over the Internet, being actively marketed by several Chinese chemical companies.

Moscow theater hostage crisis

In 2012, a team of researchers at the British chemical and biological defence laboratories at Porton Down found carfentanil and

remifentanil Remifentanil is a potent, short-acting synthetic opioid analgesic drug. It is given to patients during surgery to relieve pain and as an adjunct to an anaesthetic. Remifentanil is used for sedation as well as combined with other medications fo ...

in clothing from two British survivors of the 2002 Moscow theater hostage crisis and in the urine from a third survivor. The team concluded that the Russian military had used an aerosol mist of carfentanil and remifentanil to subdue Chechen hostage takers. Researchers had previously surmised from the available evidence that the Moscow

emergency services Emergency services and rescue services are organizations that ensure public safety and health by addressing and resolving different emergencies. Some of these agencies exist solely for addressing certain types of emergencies, while others deal w ...

had not been informed of the use of the agent, despite being instructed to bring opioid antagonists to the scene. Unaware that hundreds of patients had been exposed to high doses of strong opioids, the emergency workers failed to bring sufficient quantities of

and

to counteract the effects of carfentanil and remifentanil. As a result, one hundred twenty-five people exposed to the aerosol are confirmed to have died from

respiratory failure Respiratory failure results from inadequate gas exchange by the respiratory system, meaning that the arterial oxygen, carbon dioxide, or both cannot be kept at normal levels. A drop in the oxygen carried in the blood is known as hypoxemia; a rise ...

during the incident.

Potential as a chemical weapon

The toxicity of carfentanil in humans and its ready commercial availability has raised concerns over its potential use as a chemical

weapon of mass destruction A weapon of mass destruction (WMD) is a chemical, biological, radiological, nuclear, or any other weapon that can kill and bring significant harm to numerous individuals or cause great damage to artificial structures (e.g., buildings), natu ...

by rogue nations and

terrorist group A number of national governments and two international organizations have created lists of organizations that they designate as terrorist. The following list of designated terrorist groups lists groups designated as terrorist by current and fo ...

s. The toxicity of carfentanil has been compared to that of nerve gas.

Society and culture

Legal status

China

Carfentanil has been controlled in China since 1 March 2017. The

trade war A trade war is an economic conflict often resulting from extreme protectionism in which states raise or create tariffs or other trade barriers against each other in response to trade barriers created by the other party. If tariffs are the ex ...

between China and the United States has included controversy over the effectiveness of this control.

Germany

Carfentanil and it’s

stereoisomers In stereochemistry, stereoisomerism, or spatial isomerism, is a form of isomerism in which molecules have the same molecular formula and sequence of bonded atoms (constitution), but differ in the three-dimensional orientations of their atoms ...

and

salts In chemistry, a salt is a chemical compound consisting of an ionic assembly of positively charged cations and negatively charged anions, which results in a compound with no net electric charge. A common example is table salt, with positively c ...

are controlled by the

Betäubungsmittelgesetz The Betäubungsmittelgesetz (BtMG), generally meaning Narcotics Law, is the controlled substances law of Germany. In common with the Misuse of Drugs Act of 1971 of the United Kingdom and Controlled Substances Acts of the US and Canada, it is a ...

as a

anlage I Anlage may refer to: * Allele, a specific version of a gene, as used by Gregor Mendel * Anlage Süd, a headquarters facility of the German Third Reich in Strzyżów, Poland * Primordium, the initial clustering of embryonic cells from which a body ...

substance and can only be used with the special permission of the authorities

United States

Carfentanil is classified as Schedule II under the

Controlled Substances Act The Controlled Substances Act (CSA) is the statute establishing federal U.S. drug policy under which the manufacture, importation, possession, use, and distribution of certain substances is regulated. It was passed by the 91st United States ...

in the United States with a DEA ACSCN of 9743 and a 2016 annual aggregate manufacturing quota of 19 grams (less than 0.7 oz.).

United Kingdom

Carfentanil has been specifically controlled as a Class A drug since 1986.

References

{{Opioid receptor modulators 1974 introductions Anilides Belgian inventions Carboxylate esters Fentanyl General anesthetics Janssen Pharmaceutica Methyl esters Mu-opioid receptor agonists Piperidines Propionamides Synthetic opioids Veterinary drugs Incapacitating agents