Carfentanil or carfentanyl, formerly sold under the brand name Wildnil, is an extremely Equianalgesic opioid analgesic used in veterinary medicine to anesthesia large animals such as and .
Effects and of carfentanil in humans are similar to those of other opioids and include euphoria, relaxation, analgesia, miosis, drowsiness, sedation, bradycardia, hypotension, hypothermia, loss of consciousness, and suppression of breathing.
Carfentanil was first synthesized in 1974 by a team of chemists at Janssen Pharmaceuticals which included Paul Janssen.
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 α
2-receptor agonist as a
Tranquilizer gun for
ungulates like hippos, rhinos, and elephants, and large carnivores.
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.
Since then,
etorphine has become the standard tranquilizing agent for large mammals, with
diprenorphine as the preferred reversal agent. Diprenorphine was also used previously to reverse the effects of carfentanil.
Clinical use
Carfentanil has been used at doses of less than 7 μg as a
radiotracer for positron emission tomography
medical imaging 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 μ
1-opioid receptor over the μ
2-opioid receptor.
Carfentanil has approximately 10,000 times the
analgesia potency of
morphine, 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 were estimated to be 5.7 hours and 11.8 hours, respectively.
Chemistry
Carfentanil is an analogue of
fentanyl and is also known as (4methoxycarbonyl)fentanyl. Related analogues of fentanyl include 4phenylfentanyl,
lofentanil (3methylcarfentanyl), N-methylnorcarfentanil, R-30490 (4methoxymethylfentanyl),
sufentanil, and
thiafentanil.
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.
In 2017, a
Milwaukee,
Wisconsin 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.
Seizures by authorities
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 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 potentially lethal doses of the drug, in containers labeled as for HP LaserJet printers.
Carfentanil was not a controlled substance in China until 1 March 2017,
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
Knock-out gas of carfentanil and remifentanil to subdue
Chechnya 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. One hundred and 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
and
. The toxicity of carfentanil has been compared to that of
Nerve agent.
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.
-
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 DEA ACSCN of 9743 and a 2016 annual aggregate manufacturing quota of 19 grams (less than 0.7 oz.).
-
Carfentanil has been specifically controlled as a Class A drug since 1986.
See also
