Carfentanyl

Structural formula
General
Non-proprietary name	Carfentanil
other names	4 - [(1-Oxopropyl) phenylamino] -1- (2-phenylethyl) -4-piperidine-carboxylic acid methyl ester
Molecular formula	C 24 H 30 N 2 O 3
External identifiers / databases
CAS number 59708-52-0 (carfentanyl) 61380-27-6 (carfentanil citrate) PubChem 62156 DrugBank DB01535 Wikidata Q423386
properties
Molar mass	394.51 g mol −1
Physical state	firmly
safety instructions
GHS hazard labeling no classification available
Toxicological data	3.39 mg kg −1 ( LD 50 ,  rat ,  iv )
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Carfentanyl (also Carfentanil ) is a chemical compound that is derived from the opioid fentanyl . In contrast to other fentanyl derivatives, the substance is not used in (human) anesthesia , but in veterinary anesthesia (under the trade name Wildnil) to anesthetize large wild animals such as animals. B. Lions , Moose , Polar Bears , etc.

Effective antidotes are diprenorphine and naloxone , with which the anesthesia can be quickly reversed.

According to a report by the Associated Press, carfentanyl was legally made in China and, despite its lethal effects, was sold online around the world. Since March 2017, however, it has also been on the "List of Controlled Substances" in China, which makes uncontrolled production illegal in China as well.

Carfentanyl has been linked to deaths resulting from the end of the hostage situation in Moscow's Dubrovka Theater .

properties

Carfentanyl, along with fentanyl, alfentanil, sufentanil and remifentanil, belongs chemically to the group of 4-anilinopiperidine derivatives. The latter also include a number of so-called designer drugs . Carfentanyl is characterized by a wide therapeutic range . Its therapeutic quotient (therapy index) is around 10,000 (compared to 700 for fentanyl). In principle, overdosing is therefore easier to avoid. Little carfentanyl has to be dissolved in a sufficient amount of other liquids.

The 4-anilinopiperidine derivatives are so-called µ- or OP ₃ -receptor agonists ( opioid receptors ). As agonists, they are ligands which, due to their steric structure, bind to the μ or OP ₃ receptor and trigger an effect.

The effectiveness of carfentanyl significantly exceeds that of fentanyl and, depending on the test method, is 2206 times (mouse, hot plate , ip), 7682-10,031 times (rat, tail withdrawal , iv) up to 25,000 times (opioid-dependent monkey) Potency of morphine . Since, with alfentanil and sufentanil, highly effective analgesics were available for anesthesia, and the toxicity of carfentanyl is relatively high despite the wide therapeutic range, the substance was not used in human medicine.

Carfentanyl is more hypnosedative than fentanyl at doses that are equivalent to analgesics. The threshold dose of carfentanyl in humans, at which the first effects such as analgesia and sedation become visible, is in the range of about 1–2 micrograms, the effective dose can be 8–15 micrograms; higher doses have a strong sedative and sleep-inducing effect. Loss of consciousness occurs at doses in the range of 50-100 micrograms.

Application for stunning wild animals

Carfentanyl is mainly used for stunning wild animals, mostly as carfentanyl citrate . In wild goats, for example, an intramuscular dose of 40 μg / kg caused the animals to fall asleep after 22 ± 4.3 minutes; the elimination half- life was 5.5 hours. Carfentanyl has a respiratory-depressive effect that occurs to different degrees in different animal species . Rhinos and ostriches are very sensitive. During anesthesia, a second active ingredient is generally used to reduce the necessary dose and counteract respiratory depression.

Use as a drug

Carfentanyl became popular as a street drug in connection with the opioid crisis in the US .

Legal status

Carfentanyl is listed (as carfentanil ) in the Federal Republic of Germany in Appendix 1 of the Narcotics Act and is therefore a "non-marketable narcotic drug"; however, the substance does not fall under the international convention on psychotropic substances .

No carfentanyl-based veterinary medicinal product is approved in Germany.

literature

• PM Wax, CE Becker, SC Curry: Unexpected "gas" casualties in Moscow: a medical toxicology perspective. In: Ann Emerg Med . 41. 2003, pp. 700-705. PMID 12712038 .
• E. Freye: Opioids in Medicine. 6th edition. Berlin / Heidelberg / New York 2004, ISBN 3-540-40812-6 .

Individual evidence

1. ↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
2. ↑ Pharmaceutical Research / Drug Research . Vol. 26, 1976, p. 1548.
3. ^ Entry on carfentanyl in the ChemIDplus database of the United States National Library of Medicine (NLM), accessed on July 19, 2019.
4. ↑ Chemical weapon for sale: China's unregulated narcotic. AP, October 7, 2016.
5. ↑ WHO - CARFENTANIL - Critical Review Report - Agenda Item 4.8 , WHO, 6. – 10. November 2017.
6. ↑ James R. Riches, Robert W. Read, Robin M. Black, Nicholas J. Cooper, Christopher M. Timperley: Analysis of clothing and urine from Moscow theater siege casualties reveals carfentanil and remifentanil use . In: Journal of Analytical Toxicology . tape 36 , no. 9 , November 2012, p. 647-656 , doi : 10.1093 / jat / bks078 , PMID 23002178 .
7. ↑ ZY Lu u. a .: Synthesis and Analgesic Activity of 4-N-Propionyl-Analogs of 4-Methoxycarbonylfentanyl. In: Acta Pharm. Sinica. 25, 1990, p. 253.
8. ↑ PG Van Daele, MF De Bruyn, JM Boey, S Sanczuk, JT Agten, PA Janssen: Synthetic Analgesics: N- (1- [2-arylethyl] -4-substituted 4-piperidinyl) N-arylalkanamides. In: Arzneimittel-Forschung 26, 1976, p. 1521, DOI 10.1002 / chin. 197646236 , PMID 12769
9. ↑ WFM Van Bever u. a .: N-4-Substituted 1- (2-Arylethyl) -4-piperidinyl-N-phenylpropanamides, a Novel Series of Extremely Potent Analgesics with Unusually High Safety Margin ; Drug research. 1976; 26 (8): 1548-1551; PMID 12771 .
10. ^ V. De Vos: Immobilization of free-ranging wild animals using a new drug. In: Vet Rec. 103 (4), July 22, 1978, pp. 64-68.
11. ↑ NIDA Res. Mon. 90, 1988, p. 512.
12. ↑ Entry on carfentanil at Vetpharm, accessed on 2012-08-05.
13. ↑ carfentanil: A Dangerous New Factor in the US opioid Crisis , Ministry of Justice of the United States , the Drug Enforcement Administration Attorneys Office Eastern District of Kentucky called July 10, 2020
14. ↑ Dmitrij Fomin, Vilma Baranauskaite, Emilija Usaviciene, Alina Sumkovskaja, Sigitas Laima, Algimantas Jasulaitis, Zita Nijole Minkuviene, Sigitas Chmieliauskas, Jurgita Stasiuniene: Human deaths from drug overdoses with carfentanyl involvement - new rising problem in forensic medicine. A STROBE-compliant retrospective study . In: Medicine (Baltimore) . 97, No. 48, November 30, 2018, p. E13449. doi : 10.1097 / MD.0000000000013449 . PMID 30508965 . [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6283219/ PMC 6283219 (free full text) / PMC  PMC 6283219 (free full text)] (free full text). Retrieved July 10, 2020.
15. ↑ Nicholas Corsi, Ljubisa Dragovic: Fatal overdoses Involving carfentanil: A case series . In: Journal of Forensic Science and Medicine . 5, No. 3, September 18, 2019, pp. 147–150. doi : 10.4103 / jfsm.jfsm_74_17 . Retrieved July 10, 2020.
16. ↑ BtMG Annex I (to Section 1 Paragraph 1) narcotics that are not marketable, gesetze-im-internet.de
17. ↑ International Narcotics Control Board: List of psychotropic substances under international control. ( Memento of August 31, 2012 in the Internet Archive ) 23rd edition, August 2003.
18. ↑ vetidata (as of February 2012).