Carfentanil

Carfentanil
Clinical data
Trade names Wildnil
Synonyms 4-Carbomethoxyfentanyl
AHFS/Drugs.com International Drug Names
ATC code
  • None
Legal status
Legal status
Pharmacokinetic data
Elimination half-life 7.7 hrs
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
ChEBI
ChEMBL
Chemical and physical data
Formula C24H30N2O3
Molar mass 394.52 g·mol−1
3D model (JSmol)
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Carfentanil or carfentanyl is an analog of the synthetic opioid analgesic fentanyl.[1] For pain relief, a unit of carfentanil is 100 times as potent as the same amount of fentanyl, 5,000 times as potent as a unit of heroin and 10,000 times as potent as a unit of morphine. This is despite only having 14-135 times higher affinity for the μ receptor[2][3] It is important to note that lethality and potency are not the same, and carfentanil is less fatal than fentanyl in rats.[4]

The toxicity of carfentanil in humans and its ready commercial availability has aroused concerns over its potential use as a weapon of mass destruction by rogue nations and terrorist groups.[5]

Carfentanil was first synthesized in 1974 by a team of chemists at Janssen Pharmaceutica which included Paul Janssen.[6]

The effects of carfentanil, including overdose, can be reversed by naloxone.[7]

Typical Use

Carfentanil has been sold since 1986 under the brand name "Wildnil" for use in tranquilizer darts in combination with an α2-adrenoreceptor agonist[2] for large mammals including elk and elephants.[6][8] It is chosen for its high safety margin as the fatal dose of carfentanil is approximately the same as that of fentanyl despite much higher opioid activity.[9]

Radiolabelled [11C]carfentanil is widely used as a selective radiotracer in animal and human positron emission tomography (PET) imaging studies of the μ-opioid system due to its high affinity for receptors.[10]

Modern History

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 used an aerosol mist of carfentanil and remifentanil to subdue Chechen hostage takers.[11]

Authors of a previous paper in the Annals of Emergency Medicine surmised from the available evidence that the Moscow emergency services had not been informed of the use of the agent, but were instructed to bring opioid antagonists. Not knowing to expect hundreds of patients exposed to high doses of strong opioids, the emergency workers did not bring enough naloxone or naltrexone (the two most commonly-used opioid antagonists) to counteract the carfentanil and remifentanil and save the lives of many of the victims. 125 people exposed to the gas used in the rescue attempt are confirmed to have died from both respiratory failure and aerosol inhalation during the incident. The authors state that, assuming carfentanil and remifentanil were the only active ingredients of the knockout gas, the worst danger to the theater victims would have been apnea (loss of breathing), and that mechanical ventilation and/or treatment with opioid antagonists could have saved many lives.[12]

Importation from China

According to an Associated Press article from 2016, "Chemical weapon for sale: China's unregulated narcotic", fentanyl, carfentanil and other highly potent derivatives of fentanyl are actively marketed by several Chinese chemical companies.[5] Carfentanil was not a controlled substance in China until 1 March 2017,[13] and until then was manufactured legally and sold openly over the Internet.

Authorities in Latvia and Lithuania reported seizing carfentanil as an illicit drug in the early 2000s.[5][14] Around 2016, the US and Canada started reporting a dramatic increase in shipment of carfentanil and other strong opioid drugs to customers in North America from Chinese chemical supply firms. In June 2016 the Royal Canadian Mounted Police 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 wipe out the entire population of the country, in containers labeled as toner cartridges for Hewlett-Packard LaserJet printers. Allan Lai, an officer-in-charge at the Royal Canadian Mounted Police in Calgary who helped oversee the criminal investigation said, "With respect to carfentanil, we don't know why a substance of that potency is coming into our country."[5]

Increase in illicit use

A November 2016 article in Time, "Heroin Is Being Laced With a Terrifying New Substance: What to Know About Carfentanil", reports over 300 cases of overdose related to fentanyl and fentanyl analogues and several deaths connected to the drug since August 2016 in several of the United States, including Ohio, West Virginia, Indiana, Kentucky and Florida.[15] In 2017, a Milwaukee, Wisconsin man died from a carfentanil overdose, likely taken unknowingly with another illegal drug such as heroin or cocaine.[16] 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 (until China added it to its list of controlled substances on 1 March 2017, it was legal for Chinese firms to advertise and sell carfentanil over the Internet, offering advice to customers in other countries on how to import it illegally) and easier to make than heroin.[5] Health professionals are increasingly concerned about potential for escalated public health consequences of recreational use.[17]

Potential as a chemical weapon

The toxicity of carfentanil has been compared to that of nerve gas, according to the Associated Press' article "Chemical weapon for sale: China's unregulated narcotic". The article quoted Andrew C. Weber, Assistant US Secretary of Defense for Nuclear, Chemical and Biological Defense Programs from 2009 to 2014, as saying "It's a weapon. Companies shouldn't be just sending it to anybody." Weber added "Countries that we are concerned about were interested in using it for offensive purposes... We are also concerned that groups like ISIS could order it commercially." Weber described various ways carfentanil could be used as a weapon, such as knocking troops out and taking them hostage or killing civilians in closed spaces such as train stations.[5]

China

Carfentanil has been controlled in China since 1 March 2017.[18]

United States

Carfentanil is classified as Schedule II under the Controlled Substances Act 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.).[19]

United Kingdom

Carfentanil is specifically controlled as a Class A drug since 1986[20]

See also

References

  1. ↑ "Fentanyl drug profile". EMCDDA.
  2. 1 2 "Report on the risk assessment of methyl 1-(2-phenylethyl)-4-[phenyl(propanoyl) amino]piperidine-4-carboxylate in the framework of the Council Decision on new psychoactive substances" (PDF). 2018-07-08. p. 9.
  3. ↑ "Comparing the lethality and potency of opioid drugs". The Boston Globe. November 15, 2017. Retrieved December 14, 2017.
  4. ↑ "Report on the risk assessment of methyl 1-(2-phenylethyl)-4-[phenyl(propanoyl) amino]piperidine-4-carboxylate in the framework of the Council Decision on new psychoactive substances" (PDF). 2018-07-08. p. 64.
  5. 1 2 3 4 5 6 Kinetz, Erika; Butler, Desmond (7 October 2016). "Chemical weapon for sale: China's unregulated narcotic". AP News. New York, NY 10281 USA. The Associated Press. Retrieved 12 April 2016.
  6. 1 2 Stanley, Theodore H.; Egan, Talmage D.; Aken, Hugo Van (February 2008). "A Tribute to Dr. Paul A. J. Janssen: Entrepreneur Extraordinaire, Innovative Scientist, and Significant Contributor to Anesthesiology". Anesthesia & Analgesia. 106 (2): 451–462. doi:10.1213/ane.0b013e3181605add. PMID 18227300.
  7. ↑ "Report on the risk assessment of methyl 1-(2-phenylethyl)-4-[phenyl(propanoyl) amino]piperidine-4-carboxylate in the framework of the Council Decision on new psychoactive substances" (PDF). 2018-07-08. p. 23.
  8. ↑ Jacobson, Elliott R.; Kollias, George V.; Heard, Darryl J.; Caligiuri, Randolph (1988). "Immobilization of African Elephants with Carfentanil and Antagonism with Nalmefene and Diprenorphine". The Journal of Zoo Animal Medicine. 19 (1/2): 1–7. doi:10.2307/20094842.
  9. ↑ World Health Organisation, Carfentanil Critical Review Report (PDF), retrieved 2018-09-03
  10. ↑ "Report on the risk assessment of methyl 1-(2-phenylethyl)-4-[phenyl(propanoyl) amino]piperidine-4-carboxylate in the framework of the Council Decision on new psychoactive substances" (PDF). 2018-07-08. p. 10.
  11. ↑ Riches, James R.; Read, Robert W.; Black, Robin M.; Cooper, Nicholas J.; Timperley, Christopher M. (November 2012). "Analysis of Clothing and Urine from Moscow Theatre Siege Casualties Reveals Carfentanil and Remifentanil Use". Journal of Analytical Toxicology. 36 (9): 647–656. doi:10.1093/jat/bks078. ISSN 1945-2403. PMID 23002178.
  12. ↑ Wax, Paul M.; Becker, Charles E.; Curry, Steven C. (May 2003). "Unexpected "gas" casualties in Moscow: A medical toxicology perspective". Annals of Emergency Medicine. 41 (5): 700–705. doi:10.1067/mem.2003.148. PMID 12712038.
  13. ↑ https://www.yahoo.com/news/china-makes-deadly-opioid-carfentanil-controlled-substance-020744508.html
  14. ↑ Mounteney, Jane; Giraudon, Isabelle; Denissov, Gleb; Griffiths, Paul (July 2015). "Fentanyls: Are we missing the signs? Highly potent and on the rise in Europe". International Journal of Drug Policy. 26 (7): 626–631. doi:10.1016/j.drugpo.2015.04.003. PMID 25976511.
  15. ↑ Sanburn, Josh. "Heroin Is Being Laced With a Terrifying New Substance". TIME.com. Retrieved 2016-11-24.
  16. ↑ Stephenson, Crocker (17 April 2017). "Carfentanil, 10,000 times more potent than morphine, kills homeless man in Milwaukee". Milwaukee Journal Sentinel. Retrieved 17 April 2017.
  17. ↑ Baumann, Michael H.; G. W. Pasternak (2018). "Novel Synthetic Opioids and Overdose Deaths: Tip of the Iceberg?". Neuropsychopharmacology. 43: 216–7. doi:10.1038/npp.2017.211.
  18. ↑ "Report on the risk assessment of methyl 1-(2-phenylethyl)-4-[phenyl(propanoyl) amino]piperidine-4-carboxylate in the framework of the Council Decision on new psychoactive substances" (PDF). 2018-07-08. p. 21.
  19. ↑ "Established Aggregate Production Quotas for Schedule I and II Controlled Substances and Assessment of Annual Needs for the List I Chemicals Ephedrine, Pseudoephedrine, and Phenylpropanolamine for 2016". Federal Register. 6 October 2015.
  20. ↑ "Misuse of Drugs Act 1971 (c. 38): SCHEDULE 2: Controlled Drugs". Office of Public Sector Information. Retrieved 15 June 2009.
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