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| Trade names | Wildnil |
| Other names | (4-Methoxycarbonyl)fentanyl, R-33799 |
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| Eliminationhalf-life | 7.7 hours |
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| ECHA InfoCard | 100.352.183 |
| Chemical and physical data | |
| Formula | C24H30N2O3 |
| Molar mass | 394.515 g·mol−1 |
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Carfentanil orcarfentanyl, formerly sold under the brand nameWildnil, is an extremelypotentopioidanalgesic used inveterinary medicine toanesthetize large animals such aselephants andrhinoceroses.[1] It is astructural analogue of thesynthetic opioid analgesicfentanyl.[2] It is typically administered in this context bytranquilizer dart.[1] Carfentanil has also been used in humans toimageopioid receptors.[1] It has additionally been used as arecreational drug, typically byinjection,insufflation, orinhalation.[1] Deaths have been reported in association with carfentanil.[1][3]
Effects andside effects of carfentanil in humans are similar to those of other opioids and includeeuphoria,relaxation,pain relief,pupil constriction,drowsiness,sedation,slowed heart rate,low blood pressure,lowered body temperature,loss of consciousness, andsuppression of breathing.[1] The effects of carfentanil, includingoverdose, can be reversed by theopioid antagonistsnaloxone andnaltrexone, though higher doses than usual may be necessary compared to other opioids.[1][3][4]: 23 It acts as anultrapotent and highlyselectiveagonist of theμ-opioid receptor.[1]
Carfentanil was first synthesized in 1974 by a team of chemists atJanssen Pharmaceuticals which includedPaul Janssen.[5] It was introduced into veterinary medicine in 1986.[1] Carfentanil is legally controlled in most jurisdictions.[3]
Chosen for its hightherapeutic index, carfentanil was first sold in 1986 under the brand name "Wildnil" for use in combination with anα2-receptor agonist as atranquilizing agent[4]: 9 forungulates like hippos, rhinos, and elephants, and large carnivores.[5][6][7] Commercial production of Wildnil ceased in 2003; the drug is now available only incompounded form and not available for veterinary use due to human abuse.[6][8][9] Since then,etorphine has become the standard tranquilizing agent for large mammals, withdiprenorphine as the preferred reversal agent. Diprenorphine was also used previously to reverse the effects of carfentanil.[10]
Carfentanil has been used at doses of less than 7 μg as aradiotracer forpositron emission tomographyimaging of theμ-opioid receptor in the brain in humans.[1]
Carfentanil acts as a highlyselectiveagonist of theμ-opioid receptor.[11] It showedaffinity values (Ki) of 0.051 nM for the μ-opioid receptor, 4.7 nM for theδ-opioid receptor, and 13 nM for theκ-opioid receptor in rat brain.[11] Thus, carfentanil displayed 90- and 250-fold selectivity for the μ-opioid receptor over the δ-opioid receptor and the κ-opioid receptor, respectively.[11] 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.[9] Carfentanil appears to have higher affinity for theμ1-opioid receptor over theμ2-opioid receptor.[1] Carfentanil has approximately 10,000 times theanalgesicpotency ofmorphine, 4,000 times the potency ofheroin, and 20 to 100 times the potency of fentanyl in animal studies.[1][3][9] The effects of carfentanil are reversed byμ-opioid receptor antagonists likenaloxone andnaltrexone, though higher than normal doses of these agents may be necessary in humans due to the extremely high potency of carfentanil.[1][3]
Alipophilic chemical that can easily cross theblood–brain barrier, carfentanil has a very rapidonset of action and is longer acting than fentanyl.[4]: 9 Itselimination half-life in humans was 42 to 51 minutes following anintravenous bolus at an average dose of 1.34 μg (19 ng/kg).[1][3] However, in a case study of recreational exposure, the half-lives of carfentanil and itsmetabolitenorcarfentanil were estimated to be 5.7 hours and 11.8 hours, respectively.[1][12]
Carfentanil is ananalogue offentanyl and is also known as (4‑methoxycarbonyl)fentanyl. Related analogues of fentanyl include4‑phenylfentanyl,lofentanil (3‑methylcarfentanyl),N-methylnorcarfentanil,R-30490 (4‑methoxymethylfentanyl),sufentanil, andthiafentanil.
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 andnaltrexone was administered. The veterinarian was hospitalised but made a full recovery within a day.[6]
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, includingOhio,West Virginia,Indiana,Kentucky andFlorida.[13] In 2017, aMilwaukee,Wisconsin man died from a Carfentanil overdose, likely taken unknowingly with another illegal drug such asheroin orcocaine.[14] Carfentanil is most often taken withheroin 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.[15]
Authorities in Latvia and Lithuania reported seizing Carfentanil as an illicit drug in the early 2000s.[16]
Around 2016, the United States and Canada reported a dramatic increase in shipment of carfentanil and other strongopioid drugs to customers in North America from Chinese chemical supply firms. In June 2016, theRoyal 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 potentially lethal doses of the drug, in containers labeled astoner cartridges forHP LaserJet printers.[15]
Carfentanil was not a controlled substance in China until 1 March 2017,[17] and until then was manufactured legally and sold openly over the Internet, being actively marketed by several Chinese chemical companies.[15]
In 2012, a team of researchers at the British chemical and biological defence laboratories atPorton Down found carfentanil andremifentanil in clothing from two British survivors of the 2002Moscow theater hostage crisis and in the urine from a third survivor. The team concluded that the Russian military had used anaerosol mist of carfentanil and remifentanil to subdueChechen hostage takers.[18] Researchers had previously surmised from the available evidence that the Moscowemergency services had not been informed of the use of the agent, despite being instructed to bringopioid 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 ofnaloxone andnaltrexone to counteract the effects of carfentanil and remifentanil. One hundred and twenty-five people exposed to the aerosol are confirmed to have died fromrespiratory failure during the incident.[19]
The toxicity of carfentanil in humans and its ready commercial availability has raised concerns over its potential use as achemical weapon of mass destruction byrogue nations andterrorist groups. The toxicity of carfentanil has been compared to that ofnerve gas.[15]
Commercial production of Wildnil ceased in 2003, [now] only available in compounded [forms.] [In] rat tail withdrawal studies, the relative analgesic potency of carfentanil is approximately 10,000 times that of morphine, 4,000 times that of heroin, and 20-30 times that of fentanyl [...] Ligand receptor binding studies report [Ki values] for human opioid receptors are 0.024 nM (μ1), 3.3 nM (δ), and 43 nM (κ).
