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{{Short description|Dissociative drug}}{{Distinguish|methoxamine|methoxmetamine|methoxyketamine|methoxpropamine}}{{Use dmy dates|date=June 2020}}

factoids

| image = Methoxetamine2DCSD.svg| width = 125px| alt = | caption = | image2 = MXE.png| width2 = 200px| MedlinePlus = | legal_AU = | legal_BR = F2DATE=2023-07-24 TRANS-TITLE=COLLEGIATE BOARD RESOLUTION NO. 804 - LISTS OF NARCOTIC, PSYCHOTROPIC, PRECURSOR, AND OTHER SUBSTANCES UNDER SPECIAL CONTROLURL-STATUS=LIVE ARCHIVE-DATE=2023-08-27 PUBLISHER=DIáRIO OFICIAL DA UNIãO PUBLICATION-DATE=2023-07-25, | legal_UK = Class BPUBLISHER=FEDERALREGISTER.GOV, 21 June 2022, | legal_DE = Anlage I| legal_UN = P IIACCESS-DATE=2024-01-22, | routes_of_administration = JOURNAL = JOURNAL OF PSYCHOACTIVE DRUGS ISSUE = 3 YEAR = 2013 PMC = 3756617, 10.1080/02791072.2013.803647, | class = NMDA receptor antagonists; Dissociative hallucinogens; General anesthetics| elimination_half-life = 3–6 hourscorrect|??}}| CAS_number = 1239943-76-0| ATC_prefix = Nonecorrect|chemspider}}| DrugBank = | KEGG = C22711| ChemSpiderID = 24721792| PubChem = 52911279changed|FDA}}| UNII = ZO5ZCE6E12PCE|eticyclidine}}| C = 15| H = 21| N = 1| O = 2| SMILES = O=C1CCCCC1(C2=CC=CC(OC)=C2)NCCcorrect|chemspider}}| StdInChI = 1S/C15H21NO2/c1-3-16-15(10-5-4-9-14(15)17)12-7-6-8-13(11-12)18-2/h6-8,11,16H,3-5,9-10H2,1-2H3correct|chemspider}}| StdInChIKey = LPKTWLVEGBNOOX-UHFFFAOYSA-N}}Methoxetamine, abbreviated as MXE, is a dissociative hallucinogen that has been sold as a designer drug.JOURNAL, Morris H, Wallach J, From PCP to MXE: a comprehensive review of the non-medical use of dissociative drugs, Drug Testing and Analysis, 6, 7–8, 614–632, 2014, 24678061, 10.1002/dta.1620, It differs from many dissociatives such as ketamine and phencyclidine (PCP) that were developed as pharmaceutical drugs for use as general anesthetics in that it was designed specifically to increase the antidepressant effects of ketamine.WEB,weblink Morris H, 2011-02-11, Interview with a ketamine chemist: or to be more precise, an arylcyclohexylamine chemist, Vice Magazine, 2012-01-23, live,weblink" title="web.archive.org/web/20120130183103weblink">weblink 30 January 2012, MXE is an arylcyclohexylamine. It acts mainly as an NMDA receptor antagonist, similarly to other arylcyclohexylamines like ketamine and PCP.{{TOC limit|3}}

Recreational use

Effects

(File:Methoxetamine-2.JPG|thumb|left|225px|Methoxetamine powder.)MXE is reported to have a similar effect to ketamine.JOURNAL, Kjellgren A, Jonsson K, Methoxetamine (MXE)--a phenomenological study of experiences induced by a "legal high" from the internet, Journal of Psychoactive Drugs, 45, 3, 276–286, 2013, 24175493, 3756617, 10.1080/02791072.2013.803647, It was often believed to possess opioid properties due to its structural similarity to 3-HO-PCP, but this assumption is not supported by data, which shows insignificant affinity for the μ-opioid receptor by the compound. Recreational use of MXE has been associated with hospitalizations from high and/or combined consumption in the US and UK.JOURNAL, Wood DM, Davies S, Puchnarewicz M, Johnston A, Dargan PI, Acute toxicity associated with the recreational use of the ketamine derivative methoxetamine, European Journal of Clinical Pharmacology, 68, 5, 853–856, May 2012, 22205276, 10.1007/s00228-011-1199-9, 4084801, Acute reversible cerebellar toxicity has been documented in three cases of hospital admission due to MXE overdose, lasting for between one and four days after exposure.JOURNAL, Shields JE, Dargan PI, Wood DM, Puchnarewicz M, Davies S, Waring WS, Methoxetamine associated reversible cerebellar toxicity: three cases with analytical confirmation, Clinical Toxicology, 50, 5, 438–440, June 2012, 22578175, 10.3109/15563650.2012.683437, 40114091, MXE was designed in part in an attempt to avoid the urotoxicity associated with ketamine abuse; it was thought the compound's increased potency and reduced dose would limit the accumulation of urotoxic metabolites in the bladder. Like ketamine, MXE has been found to produce bladder inflammation and fibrosis after high dose chronic administration in mice, although the dosages used were quite large.JOURNAL, Dargan PI, Tang HC, Liang W, Wood DM, Yew DT, Three months of methoxetamine administration is associated with significant bladder and renal toxicity in mice, Clinical Toxicology, 52, 3, 176–180, March 2014, 24580056, 10.3109/15563650.2014.892605, 34284740, Reports of urotoxicity in humans have yet to appear in the medical literature.

Pharmacology

Pharmacodynamics{| class"wikitable floatright" style"font-size:small;"

weblink JOURNAL, Roth BL, Gibbons S, Arunotayanun W, Huang XP, Setola V, Treble R, Iversen L, The ketamine analogue methoxetamine and 3- and 4-methoxy analogues of phencyclidine are high affinity and selective ligands for the glutamate NMDA receptor, PLOS ONE, 8, 3, e59334, 2013, 23527166, 3602154, 10.1371/journal.pone.0059334, free, 2013PLoSO...859334R, ! Site !! Ki (nM) !! Action !! Species !! RefNMDA receptor>{{abbrN-Methyl-D-aspartate receptor}}({{abbrPhencyclidine site}})''' 259 Antagonist Human MOR10,000 >ND| DOR10,000 >ND| KOR10,000 >ND| NOP10,000 >ND| Sigma-1 receptor>σ1 >10,000 {{abbrNo data}} Guinea pig Sigma-2 receptor>σ2 >10,000 {{abbrNo data}} Rat D2 receptor>D2 >10,000 {{abbrNo data}} Human 5-HT2A receptor>5-HT2A >10,000 {{abbrNo data}} Human SERT >4812,400 (IC50>IC50)''' Inhibitor Human HONDEBRINK L, KASTEEL EE, TUKKER AM, WIJNOLTS FM, VERBOVEN AH, WESTERINK RH > TITLE = NEUROPHARMACOLOGICAL CHARACTERIZATION OF THE NEW PSYCHOACTIVE SUBSTANCE METHOXETAMINE VOLUME = 123 DATE = SEPTEMBER 2017 DOI = 10.1016/J.NEUROPHARM.2017.04.035 HDL = 1874/359894, free, NET10,00020,000 (IC50) >| DAT10,00033,000 (IC50) >| class="sortbottom" Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site.MXE acts mainly as a selective and high-affinity NMDA receptor antagonist, specifically of the dizocilpine (MK-801) site (Ki = 257 nM).JOURNAL, Zanda MT, Fadda P, Chiamulera C, Fratta W, Fattore L, Methoxetamine, a novel psychoactive substance with serious adverse pharmacological effects: a review of case reports and preclinical findings, Behavioural Pharmacology, 27, 6, 489–496, September 2016, 27128862, 10.1097/FBP.0000000000000241, 3657823, It produces ketamine-like effects.JOURNAL, Hofer KE, Grager B, Müller DM, Rauber-Lüthy C, Kupferschmidt H, Rentsch KM, Ceschi A, Ketamine-like effects after recreational use of methoxetamine, Annals of Emergency Medicine, 60, 1, 97–99, July 2012, 22237166, 10.1016/j.annemergmed.2011.11.018, In addition to antagonism of the NMDA receptor, MXE has been found to act as a serotonin reuptake inhibitor (Ki = 479 nM; IC50 = 2,400 nM). Conversely, it shows little or no effect on the reuptake of dopamine and norepinephrine (Ki and IC50 > 10,000 nM). Nonetheless, MXE has been found to activate dopaminergic neurotransmission, including in the mesolimbic reward pathway. This is a characteristic that it shares with other NMDA receptor antagonists, including ketamine, PCP, and dizocilpine (MK-801). Animal studies suggest MXE may have rapidly-acting antidepressant effects similar to those of ketamine.JOURNAL, Botanas CJ, Bryan de la Peña J, Custodio RJ, Joy Dela Peña I, Kim M, Woo T, Kim HJ, Kim HI, Chang Cho M, Lee YS, Cheong JH, 6, Methoxetamine produces rapid and sustained antidepressant effects probably via glutamatergic and serotonergic mechanisms, Neuropharmacology, 126, 121–127, November 2017, 28867363, 10.1016/j.neuropharm.2017.08.038, 30870722, A study that assessed binding of MXE at 56 sites including neurotransmitter receptors and transporters found that MXE had Ki values of >10,000 nM for all sites except the dizocilpine site of the NMDA receptor and the serotonin transporter (SERT).

Pharmacokinetics

MXE has a longer duration of action than that of ketamine.JOURNAL, Horsley RR, Lhotkova E, Hajkova K, Jurasek B, Kuchar M, Palenicek T, Detailed pharmacological evaluation of methoxetamine (MXE), a novel psychoactive ketamine analogue-Behavioural, pharmacokinetic and metabolic studies in the Wistar rat, Brain Research Bulletin, 126, Pt 1, 102–110, September 2016, 27155360, 10.1016/j.brainresbull.2016.05.002, 3955788,

Chemistry

(File:Arylcyclohexylamines.png|thumb|left|350px|Methoxetamine and related arylcyclohexylamines.)MXE is an arylcyclohexylamine and a derivative of eticyclidine (PCE). It can also be thought of as the β-Keto-derivative of 3-methoxyeticyclidine (3-MeO-PCE), or the N-ethyl homologue of methoxmetamine (MXM) and methoxpropamine (MXPr). It is closely related structurally to ketamine, and more distantly to PCP.MXE hydrochloride is soluble in ethanol up to 10 mg/ml at 25 Â°C.WEB,weblink Methoxamine (hydrochloride) Safety Data Sheet, Caymen Chemicals, 2013-07-22, live,weblink 8 April 2014,

Detection in body fluids

A forensic standard of MXE is available, and the compound has been posted on the Forendex website of potential drugs of abuse.Southern Association of Forensic Scientists WEB,weblink Methoxetamine, 10 May 2020,

History

The qualitative effects of MXE were first described online in May 2010 and the compound became commercially available on a small scale in September 2010. By November the use and sale of the MXE had increased enough for it to be formally identified by the European Monitoring Centre for Drugs and Drug Addiction. By July 2011, the EMCDDA had identified 58 websites selling the compound at a cost of 145–195 euros for 10 grams.

Society and culture

(File:Methoxetamine-3.jpg|thumb|right|225px|Methoxetamine powder.)

Media coverage

Mixmag reported in January 2012, that people in the dance music and clubbing community have given MXE the slang name 'roflcoptr'. Vice commented that it was likely that the phrase will only be used by "the same politicians, parents and journalists" who called mephedrone 'meow meow'.NEWS,weblink We Interviewed the Inventor of Roflcoptr, the New Drug Britain's Panicking About, Miller A, Vice Magazine, 2011-02-11, 2011-02-11, live,weblink" title="web.archive.org/web/20120125081300weblink">weblink 25 January 2012, After being called mexxy in UK Home Office press releases, the media adopted the name.NEWS,weblink Pair hospitalised after taking designer drug mexxy, 7 April 2014, BBC News, live,weblink" title="web.archive.org/web/20140412003310weblink">weblink 12 April 2014, NEWS,weblink London, The Guardian, Legal high drug 'mexxy' banned under new government powers, 28 March 2012, live,weblink 30 August 2017, A literature review was published in March 2012 which looked at scientific literature and information on the web. It concluded that "the online availability of information on novel psychoactive drugs, such as MXE, may constitute a pressing public health challenge. Better international collaboration levels and novel forms of intervention are necessary to tackle this fast-growing phenomenon."JOURNAL, Corazza O, Schifano F, Simonato P, Fergus S, Assi S, Stair J, Corkery J, Trincas G, Deluca P, Davey Z, Blaszko U, Demetrovics Z, Moskalewicz J, Enea A, di Melchiorre G, Mervo B, di Furia L, Farre M, Flesland L, Pasinetti M, Pezzolesi C, Pisarska A, Shapiro H, Siemann H, Skutle A, Enea A, di Melchiorre G, Sferrazza E, Torrens M, van der Kreeft P, Zummo D, Scherbaum N, 6, Phenomenon of new drugs on the Internet: the case of ketamine derivative methoxetamine, Human Psychopharmacology, 27, 2, 145–149, March 2012, 22389078, 10.1002/hup.1242, 29318833, free,

Legal status

Brazil

MXE became classified as a narcotic in Brazil in February 2014.WEB,weblink Anvisa inclui 21 substâncias em lista de drogas proibidas, 2014-07-17, pt, dead,weblink" title="web.archive.org/web/20140725174438weblink">weblink 25 July 2014,

Canada

As of January 2010 MXE is a controlled substance in Canada.WEB, 2011-01-31, Status Decision Of Controlled And Non-Controlled Substance(s),weblink dead,weblink" title="web.archive.org/web/20160409135922weblink">weblink 2016-04-09, 2021-01-29,

China

As of October 2015 MXE is a controlled substance in China.WEB,weblink 关于印发《非药用类麻醉药品和精神药品列管办法》的通知, China Food and Drug Administration, 27 September 2015, zh, 1 October 2015, 1 October 2015,weblink" title="web.archive.org/web/20151001222554weblink">weblink dead,

European Union

On 16 June 2014, the European Commission proposed that MXE be banned across the European Union, subjecting those in violation to criminal sanctions. This is following the procedure for risk-assessment and control of new psychoactive substances set up by the council: Decision 2005/387/JHA.WEB,weblink Legal highs: European Commission takes strong action with EU-wide ban on four new substances, European Commission, Midday Express, 16 June 2014, 19 August 2014, live,weblink" title="web.archive.org/web/20140820034412weblink">weblink 20 August 2014,

Israel

MXE became classified as an illegal narcotic in Israel in May 2012.WEB,weblink פקודת הסמים המסוכנים [נוסח חדש], תשל"ג-1973, 2015-02-24, he, live,weblink" title="web.archive.org/web/20150201025608weblink">weblink 1 February 2015, WEB, הודעת הסמים המסוכנים (שינוי התוספת הראשונה לפקודה) (מס" 2), התשע"ב-2012,weblink dead,weblink 2015-02-24, 2015-02-24, he,

Japan

MXE became a controlled substance in Japan from 1 July 2012, by amendment to the Pharmaceutical Affairs Law.WEB,weblink ja:薬事法指定薬物 東京都福祉保健局, 2012-06-25, ja, {{dead link|date=January 2018 |bot=InternetArchiveBot |fix-attempted=yes }}WEB, Methoxetamine Critical Report Review,weblink live,weblink 2020-11-12, 2021-01-28, World Health Organization,

Poland

MXE is a controlled substance (group II-P) making it illegal to produce, sell or possess in The Republic of Poland as of 1 July 2015.WEB,weblink Ustawa z dnia 29 lipca 2005 r. o przeciwdziałaniu narkomanii, isap.sejm.gov.pl, 7 May 2018,

Russia

MXE has been a controlled substance in Russia since October 2011.WEB,weblink Resolution of the Government of the Russian Federation on October 6, 2011 N 822, 2012-02-20, ru, live,weblink" title="web.archive.org/web/20111223053414weblink">weblink 23 December 2011,

Sweden

MXE became classified as a narcotic in Sweden in late February 2012.WEB,weblink Narkotika-klassning av sex nya substanser, 2013-11-26, sv, dead,weblink" title="web.archive.org/web/20131202234546weblink">weblink 2 December 2013,

Switzerland

MXE has been illegal in Switzerland since December 2011.WEB,weblink Ordinance on the lists of narcotic drugs, psychotropic substances, precursors and auxiliary chemicals, 2012-02-20, de, dead,weblink" title="web.archive.org/web/20120716080254weblink">weblink 16 July 2012,

United Kingdom

Prior to March 2012, MXE was not controlled by the UK's Misuse of Drugs Act.NEWS,weblink McPherson P, Health alert over drug sold as 'safe ketamine', The Independent, 2012-02-13, 2012-02-18, London, live,weblinkweblink 19 February 2012, In March 2012, the Home Office referred MXE to the Advisory Council on the Misuse of Drugs for possible temporary controlling under the powers given in the Police Reform and Social Responsibility Act 2011.WEB, 2012-03-06, Safe ketamine' referred to drug experts,weblink live,weblink" title="web.archive.org/web/20121014102252weblink">weblink 14 October 2012, 2021-01-28, gov.uk, NEWS, Johnson W, Bid to ban 'safe' drug Methoxetamine after deaths, 2012-03-06,weblink The Independent, 2012-05-12, London, live,weblinkweblink 13 May 2012, The ACMD gave their advice on 23 March, with the chair commenting that "the evidence shows that the use of methoxetamine can cause harm to users and the ACMD advises that it should be subject to a temporary class drug order."WEB, 2012-02-27, Statement of evidence - Methoxetamine,weblink live,weblink" title="web.archive.org/web/20120331033243weblink">weblink 2012-03-31, 2021-01-28, gov.uk, In April 2012, MXE was placed under temporary class drug control, which prohibited its import and sale for 12 months.WEB, Methoxetamine,weblink dead,weblink" title="web.archive.org/web/20120412100518weblink">weblink 12 April 2012, 2012-05-17, UK Home Office,

United Nations

MXE was made a schedule II drug in November 2016.NEWS, 13 November 2016, UNODC: Commission on Narcotic Drugs decision on international control of PMMA, α-PVP, 4,4'-DMAR, MXE and Phenazepam enters into force,weblink live,weblink 2020-11-08,

United States

On June 6, 2022, the U.S. Drug Enforcement Administration published a final rule placing MXE in Schedule I of the Controlled Substances Act.WEB,weblink Schedules of Controlled Substances: Placement of Methoxetamine (MXE) in Schedule I, Federal Register, 6 June 2022, 6 June 2022,

References

{{reflist}}

External links

{{Commons category}}

• Erowid.org – Methoxetamine Information

{{Drug use}}{{Hallucinogens}}{{Euphoriants}}{{Ionotropic glutamate receptor modulators}}{{Monoamine reuptake inhibitors}}