Carfentanil or carfentanyl, formerly sold under the brand name Wildnil, is an extremely potent opioid analgesic used in veterinary medicine to anesthetize large animals such as elephants and rhinoceroses.[1] It is a structural analogue of the synthetic opioid analgesic fentanyl.[2] It is typically administered in this context by tranquilizer dart.[1] Carfentanil has also been used in humans to image opioid receptors.[1] It has additionally been used as a recreational drug, typically by injection, insufflation, or inhalation.[1] Deaths have been reported in association with carfentanil.[1]
Effects and side effects of carfentanil in humans are similar to those of other opioids and include euphoria, relaxation, pain relief, pupil constriction, drowsiness, sedation, slowed heart rate, low blood pressure, lowered body temperature, loss of consciousness, and suppression of breathing.[1] The effects of carfentanil, including overdose, can be reversed by the opioid antagonists naloxone and naltrexone, though higher doses than usual may be necessary compared to other opioids.[1][3] It acts as an ultrapotent and highly selective agonist of the μ-opioid receptor.[1]
Carfentanil was first synthesized in 1974 by a team of chemists at Janssen Pharmaceuticals which included Paul Janssen.[4] It was introduced into veterinary medicine in 1986.[1] 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[3] for large ungulates, elephants, and large carnivores.[4][5] Commercial production of Wildnil ceased in 2003; the drug is now available only in compounded form and not available for veterinary use due to human abuse.[6][7] Since then, etorphine has become the standard tranquilizing agent for large mammals, with diprenorphine as the preferred reversal agent.
Pharmacology
Pharmacodynamics
Carfentanil acts as a highly selective agonist of the μ-opioid receptor.[9] It showed affinity values (Ki) 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.[9] Thus, carfentanil displayed 90- and 250-fold selectivity for the μ-opioid receptor over the δ-opioid receptor and the κ-opioid receptor, respectively.[9] 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.[7] Carfentanil appears to have higher affinity for the μ1-opioid receptor over the μ2-opioid receptor
History
The first reported case of carfentanil overdose in a person was in 1986 when a veterinarian accidentally splashed 1.5 mg carfentanil citrate into his eyes and mouth. Sedation occurred within 2 minutes and naltrexone was administered. The veterinarian was hospitalised but made a full recovery within a day.
Increase in illicit use
Over three hundred cases of overdose related to fentanyl and Carfentanil analogues were reported between August and November 2016 in several of the United States, including Ohio, West Virginia, Indiana, Kentucky and Florida.[12] In 2017, a Milwaukee, Wisconsin man died from a Carfentanil overdose, likely taken unknowingly with another illegal drug such as heroin or cocaine.[13] 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.
Seizures by authorities
Legal status
- It is scheduled as Class I drug in Canada. Class I classifications is for drugs that have no approved use in humans and poses a high risk for abuse.
- Carfentanil has been controlled in China since 1 March 2017.[3] The trade war between China and the United States has included controversy over the effectiveness of this control.[19][20][21]
- In Germany, carfentanil and its 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.
- Carfentanil is classified as Schedule II under the Controlled Substances Act in the United States with a
See also
- Opioid potency comparison
References
- Carfentanil – from an animal anesthetic to a deadly illicit drug Forensic Science International, March 2021^
- Fentanyl drug profile EMCDDA^
- 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 European Monitoring Centre for Drugs and Drug Addiction, 8 July 2018