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 opioi ...

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 to

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, 24 A ...

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 Elephantidae ...

s and rhinoceroses. It is typically administered in this context by tranquilizer dart. Carfentanil has also been used in humans for

imaging Imaging is the representation or reproduction of an object's form; especially a visual representation (i.e., the formation of an image). Imaging technology is the application of materials and methods to create, preserve, or duplicate images. ...

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 somatosta ...

s. It has additionally been used as a recreational drug, typically by injection, insufflation, or inhalation. Deaths have been reported in association with carfentanil. Effects and side effects of carfentanil in humans are similar to those of other opioids and include euphoria, 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 professionals ...

, pupil constriction,

drowsiness Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling asle ...

, sedation, slowed heart rate, low blood pressure, lowered body temperature, loss of consciousness, and suppression of breathing. The effects of carfentanil, including overdose, can be reversed by the opioid antagonists naloxone and naltrexone, 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 o ...

opioid analgesic fentanyl. It acts as an ultrapotent and highly selective agonist of the μ-opioid receptor. Carfentanil was first synthesized in 1974 by a team of chemists at Janssen Pharmaceutica which included Paul Janssen. It was introduced into veterinary medicine in 1986. Carfentanil is legally controlled in most jurisdictions.

Uses

Veterinary use

Chosen for its high therapeutic index, 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 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, ...

of the μ-opioid receptor in the brain in humans.

Pharmacology

Pharmacodynamics

Carfentanil acts as a highly selective agonist of the μ-opioid receptor. It showed affinity values (K_i) of 0.051 nM for the μ-opioid receptor, 4.7 nM for the δ-opioid receptor, and 13 nM for the κ-opioid receptor 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 of

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. Ther ...

, 4,000 times the potency of heroin, and 20 to 100 times the potency of fentanyl in animal studies. The effects of carfentanil are reversed by μ-opioid receptor antagonists like naloxone and naltrexone, though higher than normal doses of these agents may be necessary in humans due to the extremely high potency of carfentanil.

Pharmacokinetics

A lipophilic chemical that can easily cross the blood–brain barrier, carfentanil has a very rapid onset of action and is longer acting than fentanyl. Its elimination half-life in humans was 42 to 51 minutes following an intravenous bolus 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

norcarfentanil Carfentanil or carfentanyl, sold under the brand name Wildnil, is a very potent opioid analgesic which is used in veterinary medicine to anesthetize large animals such as elephants and rhinoceroses. It is typically administered in this cont ...

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

Chemistry

Carfentanil is an analogue of fentanyl 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 Thiafentanil (A-3080, Thianil) is a highly potent opioid analgesic that is an analog of fentanyl, and was invented in 1986. Its analgesic potency is slightly less than that of carfentanil (itself approximately 10,000 times the potency of morphi ...

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 ...

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and

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. In 2017, a

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, man died from a carfentanil overdose, likely taken unknowingly with another illegal drug such as heroin or cocaine. Carfentanil is most often taken with heroin 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 police, federal and national police service of ...

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 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 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 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 naloxone and naltrexone 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 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 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 Nerve agents, sometimes also called nerve gases, are a class of organic chemicals that disrupt the mechanisms by which nerves transfer messages to organs. The disruption is caused by the blocking of acetylcholinesterase (AChE), an enzyme tha ...

Society and culture

Legal status

China

Carfentanil has been controlled in China since 1 March 2017. The trade war between China and the United States has included controversy over the effectiveness of this control.

Germany

Carfentanil and it’s stereoisomers and salts are controlled by the Betäubungsmittelgesetz as a anlage I 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