Ocfentanil

Ocfentanil (INN; also called A-3217) is a potent synthetic opioid structurally related to fentanyl^[1] that was developed in the early 1990s as one of a series of potent naloxone-reversible opioids in an attempt to obtain an opioid that had better therapeutic indices in terms of cardiovascular effects and respiratory depression as compared to fentanyl.^[2] Ocfentanil was never developed for medical use despite reasonable results in human clinical trials, but subsequently started to be sold as a designer drug starting in around 2013.^[3]

Ocfentanil

Clinical data
Other names	Ocfentanyl, A-3217
ATC code	none
Legal status
Legal status	BR: Class F1 (Prohibited narcotics) CA: Schedule I DE: Anlage II (Authorized trade only, not prescriptible) UK: Class A US: Schedule I Illegal in China
Identifiers
IUPAC name N-(2-Fluorophenyl)-2-methoxy-N-[1-(2-phenylethyl)piperidin-4-yl]acetamide
CAS Number	101343-69-5 Y
PubChem CID	60575
ChemSpider	54604 N
UNII	MX52WBC8EV
CompTox Dashboard (EPA)	DTXSID00869356
Chemical and physical data
Formula	C22H27FN2O2
Molar mass	370.468 g·mol−1
3D model (JSmol)	Interactive image
SMILES COCC(=O)N(C1CCN(CC1)CCC2=CC=CC=C2)C3=CC=CC=C3F
InChI InChI=1S/C22H27FN2O2/c1-27-17-22(26)25(21-10-6-5-9-20(21)23)19-12-15-24(16-13-19)14-11-18-7-3-2-4-8-18/h2-10,19H,11-17H2,1H3 N Key:NYISTOZKVCMVEL-UHFFFAOYSA-N N
NY (what is this?)  (verify)

Study of the analgesic activity of ocfentanil using the mouse hot plate test (55 °C) gave an ED₅₀ of 0.007 mg/kg compared to 0.018 mg/kg for fentanyl; ocfentanil being approximately 2.5 times as potent as fentanyl in this test.^[4]

In human volunteers ocfentanil induces effective analgesia at 1 μg/kg, while in doses up to 3 μg/kg, analgesia and respiratory depression occurred in a dose-dependent manner. While a further study suggests that ocfentanil may be as effective as morphine in post-operative relief,^[5] Ocfentanil was also studied as a supplement to general anaesthesia, in which the researchers concluded that it appears to be similar in action to fentanyl, with 3 μg/kg of ocfentanil approximately equivalent to 5 μg/kg of fentanyl.^[6][7]

Side effects of fentanyl analogs are similar to those of fentanyl itself, which include itching, nausea and potentially serious respiratory depression, which can be life-threatening. Fentanyl analogs have killed hundreds of people throughout Europe and the former Soviet republics since the most recent resurgence in use began in Estonia in the early 2000s, and novel derivatives continue to appear.^[8][9]

Legal status

As of October 2015 Ocfentanil is a controlled substance in China.^[10]

Ocfentanil is a Schedule I controlled drug in the USA since 1. February 2018.^[11]

References

1. Filer CN, Nugent RP, Huang BS (November 1995). "The synthesis of [fluorophenyl-³H(N)] ocfentanil and [fluorophenyl-³H(N)] brifentanil". Journal of Labelled Compounds and Radiopharmaceuticals. 36 (11): 1019–1027. doi:10.1002/jlcr.2580361102. ISSN 1099-1344.
2. US 2002176888, "Oral dosage forms"
3. Misailidi N, Papoutsis I, Nikolaou P, Dona A, Spiliopoulou C, Athanaselis S (January 2018). "Fentanyls continue to replace heroin in the drug arena: the cases of ocfentanil and carfentanil". Forensic Toxicology. 36 (1): 12–32. doi:10.1007/s11419-017-0379-4. PMC 5754389. PMID 29367860.
4. Bagley JR, Kudzma LV, Lalinde NL, Colapret JA, Huang BS, Lin BS, et al. (July 1991). "Evolution of the 4-anilidopiperidine class of opioid analgesics". Medicinal Research Reviews. 11 (4): 403–36. doi:10.1002/med.2610110404. PMID 1875771. S2CID 33000913.
5. Glass P, Camporesi E, Martel D, Afifi M (1989). "The Analgesic Efficacy of A3217". Anesthesiology. 71 (Supplement): A321. doi:10.1097/00000542-198909001-00321.
6. Fletcher JE, Sebel PS, Murphy MR, Mick SA, Fein S (November 1991). "Comparison of ocfentanil and fentanyl as supplements to general anesthesia". Anesthesia and Analgesia. 73 (5): 622–6. doi:10.1213/00000539-199111000-00019. PMID 1952145. S2CID 40909537.
7. Ebrahim Z (1991). "Multiple dose evaluation of the efficacy of ocfentanil hydrochloride (A3217) to produce postoperative analgesia". Anesthesia and Analgesia. 72: S63. doi:10.1213/00000539-199102001-00001.
8. Mounteney J, Giraudon I, Denissov G, Griffiths P (July 2015). "Fentanyls: Are we missing the signs? Highly potent and on the rise in Europe". The International Journal on Drug Policy. 26 (7): 626–31. doi:10.1016/j.drugpo.2015.04.003. PMID 25976511.
9. Dussy FE, Hangartner S, Hamberg C, Berchtold C, Scherer U, Schlotterbeck G, et al. (November 2016). "An Acute Ocfentanil Fatality: A Case Report with Postmortem Concentrations". Journal of Analytical Toxicology. 40 (9): 761–766. doi:10.1093/jat/bkw096. PMID 27650310.
10. "关于印发《非药用类麻醉药品和精神药品列管办法》的通知" (in Chinese). China Food and Drug Administration. 27 September 2015. Archived from the original on 1 October 2015. Retrieved 1 October 2015.
11. "Schedules of Controlled Substances: Temporary Placement of Seven Fentanyl-Related Substances in Schedule I". Federal Register. 1 February 2018.