Ephenidine

{{Drugbox

| IUPAC_name = N-Ethyl-1,2-diphenylethylamine

| image = Ephenidine.svg

| image_class = skin-invert-image

| tradename =

| pregnancy_AU =

| pregnancy_US =

| pregnancy_category =

| legal_AU = Unscheduled

| legal_CA = Schedule I

| legal_DE = NpSG

| legal_UK = PSA

| legal_status = Illegal in Sweden

| routes_of_administration =

| bioavailability =

| protein_bound =

| metabolism =

| elimination_half-life =

| excretion =

| CAS_number_Ref =

| CAS_number = 60951-19-1

| CAS_number2 = 6272-97-5

| index_label =

| index2_label = HCl

| ATC_prefix =

| ATC_suffix =

| PubChem = 110821

| PubChem2 = 110820

| ChemSpiderID = 99470

| ChemSpiderID2 = 99469

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

| UNII = NG69VG2948

| C=16 | H=19 | N=1

| melting_point =

| smiles = CCNC(CC1=CC=CC=C1)C2=CC=CC=C2

| smiles2 = CCNC(CC1=CC=CC=C1)C2=CC=CC=C2.Cl

| StdInChI = 1S/C16H19N/c1-2-17-16(15-11-7-4-8-12-15)13-14-9-5-3-6-10-14/h3-12,16-17H,2,13H2,1H3

| StdInChI2 = 1S/C16H19N.ClH/c1-2-17-16(15-11-7-4-8-12-15)13-14-9-5-3-6-10-14;/h3-12,16-17H,2,13H2,1H3;1H

| StdInChIKey = IGFZMQXEKIZPDR-UHFFFAOYSA-N

| StdInChIKey2 = WOSDTAOMYCNNJE-UHFFFAOYSA-N

}}

Ephenidine (also known as NEDPA and EPE) is a dissociative anesthetic that has been sold online as a designer drug.{{cite journal | vauthors = Morris H, Wallach J | title = From PCP to MXE: a comprehensive review of the non-medical use of dissociative drugs | journal = Drug Testing and Analysis | volume = 6 | issue = 7–8 | pages = 614–32 | date = July–August 2014 | pmid = 24678061 | doi = 10.1002/dta.1620 }}{{cite journal | vauthors = Meyer MR, Orschiedt T, Maurer HH | title = Michaelis-Menten kinetic analysis of drugs of abuse to estimate their affinity to human P-glycoprotein | journal = Toxicology Letters | volume = 217 | issue = 2 | pages = 137–42 | date = February 2013 | pmid = 23273999 | doi = 10.1016/j.toxlet.2012.12.012 }} It is illegal in some countries as a structural isomer of the banned opioid drug lefetamine, but has been sold in countries where it is not yet banned.{{cite journal | vauthors = Wink CS, Meyer GM, Wissenbach DK, Jacobsen-Bauer A, Meyer MR, Maurer HH | title = Lefetamine-derived designer drugs N-ethyl-1,2-diphenylethylamine (NEDPA) and N-iso-propyl-1,2-diphenylethylamine (NPDPA): metabolism and detectability in rat urine using GC-MS, LC-MSn and LC-HR-MS/MS | journal = Drug Testing and Analysis | volume = 6 | issue = 10 | pages = 1038–48 | date = October 2014 | pmid = 24591097 | doi = 10.1002/dta.1621 }}{{cite journal | vauthors = Wink CS, Meyer GM, Meyer MR, Maurer HH | title = Toxicokinetics of lefetamine and derived diphenylethylamine designer drugs-Contribution of human cytochrome P450 isozymes to their main phase I metabolic steps | journal = Toxicology Letters | volume = 238 | issue = 3 | pages = 39–44 | date = November 2015 | pmid = 26276083 | doi = 10.1016/j.toxlet.2015.08.012 }}

Pharmacology

=Pharmacodynamics=

Ephenidine and related diarylethylamines have been studied in vitro as treatments for neurotoxic injuries, and are antagonists of the NMDA receptor (K_i = 66.4 nM for ephenidine).{{cite web | url=https://www.surechembl.org/document/EP-0346791-B1/ | title=Patent EP 0346791 - 1,2-diarylethylamines for treatment of neurotoxic injury | via=SureChEMBL | publisher=G.D. Searle, LLC | date=6 April 1994 | vauthors = Gray NM, Cheng BK | access-date=11 August 2016 | archive-date=20 September 2018 | archive-url=https://web.archive.org/web/20180920170031/https://www.surechembl.org/document/EP-0346791-B1/ | url-status=live }}{{cite journal | vauthors = Berger ML, Schweifer A, Rebernik P, Hammerschmidt F | title = NMDA receptor affinities of 1,2-diphenylethylamine and 1-(1,2-diphenylethyl)piperidine enantiomers and of related compounds | journal = Bioorganic & Medicinal Chemistry | volume = 17 | issue = 9 | pages = 3456–62 | date = May 2009 | pmid = 19345586 | doi = 10.1016/j.bmc.2009.03.025 }}{{cite journal | vauthors = Wallach J, Kavanagh PV, McLaughlin G, Morris N, Power JD, Elliott SP, Mercier MS, Lodge D, Morris H, Dempster NM, Brandt SD | display-authors = 6 | title = Preparation and characterization of the 'research chemical' diphenidine, its pyrrolidine analogue, and their 2,2-diphenylethyl isomers | journal = Drug Testing and Analysis | volume = 7 | issue = 5 | pages = 358–67 | date = May 2015 | pmid = 25044512 | doi = 10.1002/dta.1689 | url = http://researchonline.ljmu.ac.uk/id/eprint/3408/1/DTA-14-0117.R1.pdf | access-date = 2021-05-31 | archive-date = 2020-03-07 | archive-url = https://web.archive.org/web/20200307114648/http://researchonline.ljmu.ac.uk/id/eprint/3408/1/DTA-14-0117.R1.pdf | url-status = live }}{{cite journal | vauthors = Thurkauf A, Monn J, Mattson MV, Jacobson AE, Rice KC | title = Structural and conformational aspects of the binding of aryl-alkyl amines to the phencyclidine binding site | journal = NIDA Research Monograph | volume = 95 | pages = 51–6 | date = 1989 | pmid = 2561843 | url = http://archives.drugabuse.gov/pdf/monographs/95.pdf | access-date = 2016-08-11 | url-status = dead | archive-url = https://web.archive.org/web/20170823121157/https://archives.drugabuse.gov/pdf/monographs/95.pdf | archive-date = 2017-08-23 }}{{cite journal | vauthors = Goodson LH, Wiegand CJ, Splitter JS | title = Analgesics; n-alkylated-1,2-diphenylethylamines prepared by the Leuckart reaction | journal = Journal of the American Chemical Society | volume = 68 | issue = 11 | pages = 2174–2175 | date = November 1946 | pmid = 21002222 | doi = 10.1021/ja01215a018 | bibcode = 1946JAChS..68.2174G }} Ephenidine also possesses weaker affinity for dopamine and norepinephrine transporters (379 nM and 841 nM, respectively) as well as σ₁R (629 nM) and σ₂R (722 nM) binding sites.{{cite journal | vauthors = Kang H, Park P, Bortolotto ZA, Brandt SD, Colestock T, Wallach J, Collingridge GL, Lodge D | display-authors = 6 | title = Ephenidine: A new psychoactive agent with ketamine-like NMDA receptor antagonist properties | journal = Neuropharmacology | volume = 112 | issue = Pt A | pages = 144–149 | date = January 2017 | pmid = 27520396 | pmc = 5084681 | doi = 10.1016/j.neuropharm.2016.08.004 }}

=Pharmacokinetics=

=Metabolism=

Ephenidine's metabolic pathway consists of N-oxidation, N-dealkylation, mono- and bis-hydroxylation of the benzyl ring, and hydroxylation of the phenyl ring only after N-dealkylation. The dihydroxy metabolites were conjugated by methylation of one hydroxy group, and hydroxy metabolites by glucuronidation or sulfation.{{cite journal | vauthors = Wink CS, Meyer GM, Zapp J, Maurer HH | title = Lefetamine, a controlled drug and pharmaceutical lead of new designer drugs: synthesis, metabolism, and detectability in urine and human liver preparations using GC-MS, LC-MS(n), and LC-high resolution-MS/MS | journal = Analytical and Bioanalytical Chemistry | volume = 407 | issue = 6 | pages = 1545–57 | date = February 2015 | pmid = 25577353 | doi = 10.1007/s00216-014-8414-3 | s2cid = 26014465 }}

Chemistry

Ephenidine reacts with reagent testing kits to give a semi-unique array of colors which can be used to aid its identification.

class="wikitable" \|+ Final colors produced by reagent tests{{cite web \| url=https://www.reagent-tests.uk/blog/ephenidine-reaction-results-with-various-reagent-tests/ \| title=Ephenidine reaction results with various reagent tests \| publisher=Reagent Tests UK \| date=17 January 2016 \| access-date=23 January 2016 \| archive-date=20 September 2018 \| archive-url=https://web.archive.org/web/20180920170648/https://www.reagent-tests.uk/blog/ephenidine-reaction-results-with-various-reagent-tests/ \| url-status=live }}
Reagent !Reaction color
Marquis \| Orange > Brown
Mandelin \| Green
Liebermann \| Deep red > Brown (fast)
Froehde \| Light Yellow

class="wikitable"

|+ Final colors produced by reagent tests{{cite web | url=https://www.reagent-tests.uk/blog/ephenidine-reaction-results-with-various-reagent-tests/ | title=Ephenidine reaction results with various reagent tests | publisher=Reagent Tests UK | date=17 January 2016 | access-date=23 January 2016 | archive-date=20 September 2018 | archive-url=https://web.archive.org/web/20180920170648/https://www.reagent-tests.uk/blog/ephenidine-reaction-results-with-various-reagent-tests/ | url-status=live }}

Reagent

!Reaction color

Marquis

| Orange > Brown

Mandelin

| Green

Liebermann

| Deep red > Brown (fast)

Froehde

| Light Yellow

Society and culture

Sweden's public health agency suggested that ephenidine be classified as a hazardous substance on 1 June, 2015. Due to that suggestion, ephenidine became a scheduled substance, in Sweden, as of 18 August, 2015.{{cite web | url=https://www.folkhalsomyndigheten.se/nyheter-och-press/nyhetsarkiv/2015/juni/23-nya-amnen-kan-klassas-som-narkotika-eller-halsofarlig-vara | title=23 nya ämnen kan klassas som narkotika eller hälsofarlig vara | publisher=Folkhälsomyndigheten | language=sv | date=1 June 2015 | access-date=15 August 2016 | archive-date=17 June 2019 | archive-url=https://web.archive.org/web/20190617163154/https://www.folkhalsomyndigheten.se/nyheter-och-press/nyhetsarkiv/2015/juni/23-nya-amnen-kan-klassas-som-narkotika-eller-halsofarlig-vara/ | url-status=live }}

In 2016, Canada added MT-45 and "its salts, derivatives, isomers and analogues" to the Schedule I controlled substance list, and explicitly included ephenidine.{{cite journal | url=http://www.gazette.gc.ca/rp-pr/p2/2016/2016-06-01/html/sor-dors106-eng.php | title=Regulations Amending the Food and Drug Regulations (Parts G and J — Lefetamine, AH-7921, MT-45 and W-18) | vauthors = Arsenault D | journal=Canada Gazette | date=1 June 2016 | volume=150 | issue=11 | access-date=2016-11-17 | archive-date=2017-12-02 | archive-url=https://web.archive.org/web/20171202203151/http://www.gazette.gc.ca/rp-pr/p2/2016/2016-06-01/html/sor-dors106-eng.php | url-status=live }} Possession without legal authority can result in maximum 7 years imprisonment.