ocfentanil

{{Short description|Synthetic opioid}}

{{Drugbox

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 444480071

| IUPAC_name = N-(2-Fluorophenyl)-2-methoxy-N-[1-(2-phenylethyl)piperidin-4-yl]acetamide

| image = Ocfentanil.svg

| image_class = skin-invert-image

| image2 = Ocfentanil 3D BS.png

| image_class2 = bg_transparent

| tradename =

| pregnancy_AU =

| pregnancy_US =

| pregnancy_category =

| legal_AU =

| legal_BR = F1

| legal_CA = Schedule I

| legal_DE = Anlage II

| legal_UK = Class A

| legal_US = Schedule I

| legal_status = Illegal in China

| routes_of_administration =

| bioavailability =

| protein_bound =

| metabolism =

| elimination_half-life =

| excretion =

| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 101343-69-5

| ATC_prefix = none

| ATC_suffix =

| PubChem = 60575

| ChEBI = 183384

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank =

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = MX52WBC8EV

| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}

| ChemSpiderID = 54604

| C=22 | H=27 | F=1 | N=2 | O=2

| smiles = COCC(=O)N(C1CCN(CC1)CCC2=CC=CC=C2)C3=CC=CC=C3F

| StdInChI_Ref = {{stdinchicite|changed|chemspider}}

| StdInChI = 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

| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}

| StdInChIKey = NYISTOZKVCMVEL-UHFFFAOYSA-N

| synonyms = Ocfentanyl, A-3217

}}

Ocfentanil (INN; also called A-3217) is a potent synthetic opioid structurally related to fentanyl{{cite journal | vauthors = Filer CN, Nugent RP, Huang BS|title=The synthesis of [fluorophenyl-³H(N)] ocfentanil and [fluorophenyl-³H(N)] brifentanil|journal=Journal of Labelled Compounds and Radiopharmaceuticals|date=November 1995|issn=1099-1344|pages=1019–1027|volume=36|issue=11|doi=10.1002/jlcr.2580361102}} that was developed in the early 1990s as one of a series of potent naloxone-reversible opioids. The aim was to obtain an opioid with better therapeutic indices regarding cardiovascular effects and respiratory depression compared to fentanyl.{{cite patent | country = US | number = 2002176888 | title = Oral dosage forms }} Despite showing reasonable results in human clinical trials, Ocfentanil was never developed for medical use. However, it subsequently began to be sold as a designer drug around 2013.{{cite journal | vauthors = Misailidi N, Papoutsis I, Nikolaou P, Dona A, Spiliopoulou C, Athanaselis S | title = Fentanyls continue to replace heroin in the drug arena: the cases of ocfentanil and carfentanil | journal = Forensic Toxicology | volume = 36 | issue = 1 | pages = 12–32 | date = January 2018 | pmid = 29367860 | pmc = 5754389 | doi = 10.1007/s11419-017-0379-4 }}

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, indicating that ocfentanil is approximately 2.5 times as potent as fentanyl in this test.{{cite journal | vauthors = Bagley JR, Kudzma LV, Lalinde NL, Colapret JA, Huang BS, Lin BS, Jerussi TP, Benvenga MJ, Doorley BM, Ossipov MH | display-authors = 6 | title = Evolution of the 4-anilidopiperidine class of opioid analgesics | journal = Medicinal Research Reviews | volume = 11 | issue = 4 | pages = 403–36 | date = July 1991 | pmid = 1875771 | doi = 10.1002/med.2610110404 | s2cid = 33000913 }}

In human volunteers, ocfentanil induces effective analgesia at 1 μg/kg, while at doses up to 3 μg/kg, analgesia and respiratory depression occurred in a dose-dependent manner. One study suggests ocfentanil may be as effective as morphine in post-operative relief,{{cite journal| vauthors = Glass P, Camporesi E, Martel D, Afifi M |title=The Analgesic Efficacy of A3217|journal=Anesthesiology|volume=71|issue=Supplement|doi=10.1097/00000542-198909001-00321|year=1989|page=A321}} and it has also been studied as a supplement to general anesthesia. 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.{{cite journal | vauthors = Fletcher JE, Sebel PS, Murphy MR, Mick SA, Fein S | s2cid = 40909537 | title = Comparison of ocfentanil and fentanyl as supplements to general anesthesia | journal = Anesthesia and Analgesia | volume = 73 | issue = 5 | pages = 622–6 | date = November 1991 | pmid = 1952145 | doi = 10.1213/00000539-199111000-00019 | doi-access = free }}{{cite journal | title=Multiple dose evaluation of the efficacy of ocfentanil hydrochloride (A3217) to produce postoperative analgesia. | author=Ebrahim Z | journal=Anesthesia and Analgesia | year=1991 | volume=72|page=S63|doi=10.1213/00000539-199102001-00001}}

Side effects of fentanyl analogs are similar to those of fentanyl itself, including 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.{{cite journal | vauthors = Mounteney J, Giraudon I, Denissov G, Griffiths P | title = Fentanyls: Are we missing the signs? Highly potent and on the rise in Europe | journal = The International Journal on Drug Policy | volume = 26 | issue = 7 | pages = 626–31 | date = July 2015 | pmid = 25976511 | doi = 10.1016/j.drugpo.2015.04.003 }}{{cite journal | vauthors = Dussy FE, Hangartner S, Hamberg C, Berchtold C, Scherer U, Schlotterbeck G, Wyler D, Briellmann TA | display-authors = 6 | title = An Acute Ocfentanil Fatality: A Case Report with Postmortem Concentrations | journal = Journal of Analytical Toxicology | volume = 40 | issue = 9 | pages = 761–766 | date = November 2016 | pmid = 27650310 | doi = 10.1093/jat/bkw096 | doi-access = free }}