:Ohmefentanyl

{{Short description|Opioid analgesic}}

{{Drugbox

| Watchedfields = changed

| verifiedrevid = 447755463

| IUPAC_name = N-[1-(2-hydroxy-2-phenylethyl)-3-methylpiperidin-4-yl]-N-phenylpropanamide

| image = Ohmefentanyl.svg

| width = 220px

| image2 = Ohmfentanyl 3R,4S,βS 3D BS.png

| width2 = 220px

| tradename =

| pregnancy_AU =

| pregnancy_US =

| pregnancy_category =

| legal_AU =

| legal_BR = F1

| legal_CA = Schedule I

| legal_US = Schedule I

| legal_UK = Class A

| legal_DE = Anlage I

| legal_UN = P I

| routes_of_administration =

| bioavailability =

| protein_bound =

| metabolism =

| elimination_half-life =

| excretion =

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

| CAS_number = 78995-14-9

| ATC_prefix = none

| ATC_suffix =

| PubChem = 62279

| DrugBank = DB01570

| KEGG = C22750

| ChEBI = 194294

| ChEMBL = 333410

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 56080

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

| UNII = Y8263089ZX

| C=23 | H=30 | N=2 | O=2

| smiles = CCC(=O)N(c1ccccc1)C2CCN(CC2C)CC(O)c3ccccc3

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C23H30N2O2/c1-3-23(27)25(20-12-8-5-9-13-20)21-14-15-24(16-18(21)2)17-22(26)19-10-6-4-7-11-19/h4-13,18,21-22,26H,3,14-17H2,1-2H3

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = FRPRNNRJTCONEC-UHFFFAOYSA-N

| melting_point =

| melting_high =

}}

Ohmefentanyl (also known as β-hydroxy-3-methylfentanyl, OMF and RTI-4614-4){{cite journal | vauthors = Rothman RB, Xu H, Seggel M, Jacobson AE, Rice KC, Brine GA, Carroll FI | title = RTI-4614-4: an analog of (+)-cis-3-methylfentanyl with a 27,000-fold binding selectivity for mu versus delta opioid binding sites | journal = Life Sciences | volume = 48 | issue = 23 | pages = PL111–PL116 | date = April 1991 | pmid = 1646357 | doi = 10.1016/0024-3205(91)90346-D }} is an extremely potent opioid analgesic drug which selectively binds to the μ-opioid receptor.{{cite journal | vauthors = Brine GA, Stark PA, Liu Y, Carroll FI, Singh P, Xu H, Rothman RB | title = Enantiomers of diastereomeric cis-N-[1-(2-hydroxy-2-phenylethyl)- 3-methyl-4-piperidyl]-N-phenylpropanamides: synthesis, X-ray analysis, and biological activities | journal = Journal of Medicinal Chemistry | volume = 38 | issue = 9 | pages = 1547–1557 | date = April 1995 | pmid = 7739013 | doi = 10.1021/jm00009a015 }}{{cite journal | vauthors = Wang ZX, Zhu YC, Jin WQ, Chen XJ, Chen J, Ji RY, Chi ZQ | title = Stereoisomers of N-[1-hydroxy-(2-phenylethyl)-3-methyl-4-piperidyl]- N-phenylpropanamide: synthesis, stereochemistry, analgesic activity, and opioid receptor binding characteristics | journal = Journal of Medicinal Chemistry | volume = 38 | issue = 18 | pages = 3652–3659 | date = September 1995 | pmid = 7658453 | doi = 10.1021/jm00018a026 }}

There are eight possible stereoisomers of ohmefentanyl. These stereoisomers are among the most potent μ-opioid receptor agonists known, comparable to super-potent opioids such as carfentanil and etorphine which are only legally used for tranquilizing large animals such as elephants in veterinary medicine. In mouse studies, the most active stereoisomer, 3R,4S,βS-ohmefentanyl, was 28 times more powerful as a painkiller than fentanyl, the chemical from which it is derived, and 6300 times more powerful than morphine.{{cite web | url=http://apps.dtic.mil/dtic/tr/fulltext/u2/a199595.pdf | archive-url=https://web.archive.org/web/20140714151411/http://www.dtic.mil/dtic/tr/fulltext/u2/a199595.pdf | url-status=live | archive-date=July 14, 2014 | title=The Metabolites of Fentanyl and its Derivatives | publisher=U.S. Army Chemical Research, Development and Engineering Center, Aberdeen Proving Ground, MD | date=September 1988 | author=H. D. Banks, C. P. Ferguson}}{{cite journal | vauthors = Jin WQ, Xu H, Zhu YC, Fang SN, Xia XL, Huang ZM, Ge BL, Chi ZQ | display-authors = 6 | title = Studies on synthesis and relationship between analgesic activity and receptor affinity for 3-methyl fentanyl derivatives | journal = Scientia Sinica | volume = 24 | issue = 5 | pages = 710–720 | date = May 1981 | pmid = 6264594 }}{{cite journal | vauthors = Zhu YC, Wu RQ, Chou DP, Huang ZM | title = [Studies on potent analgesics. VII. Synthesis and analgesic activity of diastereoisomers of 1-beta-hydroxy-3-methylfentanyl (7302) and related compounds] | journal = Yao Xue Xue Bao = Acta Pharmaceutica Sinica | volume = 18 | issue = 12 | pages = 900–904 | date = December 1983 | pmid = 6679170 }}{{cite journal | vauthors = Guo GW, He Y, Jin WQ, Zou Y, Zhu YC, Chi ZQ | title = Comparison of physical dependence of ohmefentanyl stereoisomers in mice | journal = Life Sciences | volume = 67 | issue = 2 | pages = 113–120 | date = June 2000 | pmid = 10901279 | doi = 10.1016/S0024-3205(00)00617-2 }} Ohmefentanyl has three stereogenic centers and eight stereoisomers, which are named F9201–F9208. Researchers are studying the different pharmaceutical properties of these isomers.{{cite journal | vauthors = Liu ZH, He Y, Jin WQ, Chen XJ, Shen QX, Chi ZQ | title = Effect of chronic treatment of ohmefentanyl stereoisomers on cyclic AMP formation in Sf9 insect cells expressing human mu-opioid receptors | journal = Life Sciences | volume = 74 | issue = 24 | pages = 3001–3008 | date = April 2004 | pmid = 15051423 | doi = 10.1016/j.lfs.2003.10.027 }}

The 4″-fluoro analogue (i.e., substituted on the phenethyl ring) of the 3R,4S,βS isomer of ohmefentanyl is one of the most potent opioid agonists yet discovered, possessing an analgesic potency approximately 18,000 times that of morphine.{{cite journal | vauthors = Yong Z, Hao W, Weifang Y, Qiyuan D, Xinjian C, Wenqiao J, Youcheng Z | title = Synthesis and analgesic activity of stereoisomers of cis-fluoro-ohmefentanyl | journal = Die Pharmazie | volume = 58 | issue = 5 | pages = 300–302 | date = May 2003 | pmid = 12779044 | url = http://www.ingentaconnect.com/contentone/govi/pharmaz/2003/00000058/00000005/art00002 }} Other analogues with potency higher than that of ohmefentanyl itself include the 2′-fluoro derivative (i.e., substituted on the aniline phenyl ring), and derivatives where the N-propionyl group was replaced by N-methoxyacetyl or 2-furamide groups, or a carboethoxy group is added to the 4-position of the piperidine ring. The latter is listed as being up to 30,000 times more potent than morphine.{{cite journal | title=Ohmefentanyl and its stereoisomers: Chemistry and pharmacology | vauthors=Brine GA,Carroll FI, Richardson-Leibert TM,Xu H,Rothman RB | journal=Current Medicinal Chemistry | date=August 1997 | volume=4 | issue=4 | pages=247–270 | doi=10.2174/0929867304666220313115017 | issn=0929-8673}}

Side effects of fentanyl analogues are similar to those of fentanyl itself, which include itching, nausea and potentially serious respiratory depression, which can be life-threatening. Illicitly used fentanyl analogues 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 = 626–631 | date = July 2015 | pmid = 25976511 | doi = 10.1016/j.drugpo.2015.04.003 }}

File:Fentanyl numbering.svg

File:OMF.png

File:Ohmfentanyl stereoisomers.png