Methoxphenidine
{{Short description|Chemical compound}}
{{Drugbox
| IUPAC_name = (±)-1-[1-(2-methoxyphenyl)-2-phenylethyl]piperidine
| image = Methoxphenidine structure.svg
| tradename =
| pregnancy_AU =
| pregnancy_US =
| pregnancy_category =
| legal_BR = F2
| legal_CA = Schedule I
| legal_DE = NpSG
| legal_UK = PSA
| legal_status = Illegal in China and Sweden
| routes_of_administration = Oral, Rectal
| bioavailability =
| protein_bound =
| metabolism =
| elimination_half-life =
| excretion =
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 127529-46-8
| ATC_prefix =
| ATC_suffix =
| PubChem = 67833251
| UNII = H2W7A6GZGX
| ChemSpiderID = 52085156
| smiles = COC1=C(C=CC=C1)C(CC2=CC=CC=C2)N3CCCCC3
| StdInChI = 1S/C20H25NO/c1-22-20-13-7-6-12-18(20)19(21-14-8-3-9-15-21)16-17-10-4-2-5-11-17/h2,4-7,10-13,19H,3,8-9,14-16H2,1H3
| StdInChIKey = QXXCUXIRBHSITD-UHFFFAOYSA-N
| C=20 | H=25 | N=1 | O=1
}}
Methoxphenidine (methoxydiphenidine, 2-MeO-Diphenidine, MXP) is a dissociative of the diarylethylamine class 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 = 614–632 | date = July–August 2014 | pmid = 24678061 | doi = 10.1002/dta.1620 }}{{cite journal | vauthors = Van Hout MC, Hearne E | title = "Word of mouse": indigenous harm reduction and online consumerism of the synthetic compound methoxphenidine | journal = Journal of Psychoactive Drugs | volume = 47 | issue = 1 | pages = 30–41 | date = January–March 2015 | pmid = 25715070 | doi = 10.1080/02791072.2014.974002 | s2cid = 6204908 }} Methoxphenidine was first reported in a 1989 patent where it was tested as a treatment for neurotoxic injury.{{cite patent | url=https://www.google.com/patents/EP0346791B1 | country = EP | number = 0346791 | title = 1,2-diarylethylamines for treatment of neurotoxic injury | inventor = Gray NM, Cheng BK | assign = GD Searle LLC | gdate = 6 April 1994 }} Shortly after the 2013 UK ban on arylcyclohexylamines methoxphenidine and the related compound diphenidine became available on the gray market, where it has been encountered as a powder and in tablet form.{{cite journal | vauthors = McLaughlin G, Morris N, Kavanagh PV, Power JD, O'Brien J, Talbot B, Elliott SP, Wallach J, Hoang K, Morris H, Brandt SD | display-authors = 6 | title = Test purchase, synthesis, and characterization of 2-methoxydiphenidine (MXP) and differentiation from its meta- and para-substituted isomers | journal = Drug Testing and Analysis | volume = 8 | issue = 1 | pages = 98–109 | date = January 2016 | pmid = 25873326 | doi = 10.1002/dta.1800 | url = http://researchonline.ljmu.ac.uk/id/eprint/3276/1/DTA-15-0028.R1.pdf | access-date = 2021-05-31 | url-status = live | s2cid = 33626099 | archive-url = https://web.archive.org/web/20200309182524/http://researchonline.ljmu.ac.uk/id/eprint/3276/1/DTA-15-0028.R1.pdf | archive-date = 2020-03-09 }} Though diphenidine possesses higher affinity for the NMDA receptor, anecdotal reports suggest methoxphenidine has greater oral potency. Of the three isomeric anisyl-substituents methoxphenidine has affinity for the NMDA receptor that is higher than 4-MeO-diphenidine but lower than 3-MeO-diphenidine,{{cite journal | vauthors = Sahai MA, Davidson C, Dutta N, Opacka-Juffry J | title = Mechanistic Insights into the Stimulant Properties of Novel Psychoactive Substances (NPS) and Their Discrimination by the Dopamine Transporter-In Silico and In Vitro Exploration of Dissociative Diarylethylamines | journal = Brain Sciences | volume = 8 | issue = 4 | pages = 63 | date = April 2018 | pmid = 29642450 | pmc = 5924399 | doi = 10.3390/brainsci8040063 | doi-access = free }} a structure–activity relationship shared by the arylcyclohexylamines.{{cite journal | vauthors = Wallach J, Kang H, Colestock T, Morris H, Bortolotto ZA, Collingridge GL, Lodge D, Halberstadt AL, Brandt SD, Adejare A | display-authors = 6 | title = Pharmacological Investigations of the Dissociative 'Legal Highs' Diphenidine, Methoxphenidine and Analogues | journal = PLOS ONE | volume = 11 | issue = 6 | pages = e0157021 | date = June 2016 | pmid = 27314670 | pmc = 4912077 | doi = 10.1371/journal.pone.0157021 | doi-access = free | bibcode = 2016PLoSO..1157021W }}
Side effects
Acute methoxphenidine intoxication has been reported to produce confusion, hypertension, and tachycardia that was responsive to treatment with intravenous lorazepam,{{cite journal | vauthors = Hofer KE, Degrandi C, Müller DM, Zürrer-Härdi U, Wahl S, Rauber-Lüthy C, Ceschi A | title = Acute toxicity associated with the recreational use of the novel dissociative psychoactive substance methoxphenidine | journal = Clinical Toxicology | volume = 52 | issue = 10 | pages = 1288–1291 | date = December 2014 | pmid = 25350467 | doi = 10.3109/15563650.2014.974264 | url = http://www.zora.uzh.ch/id/eprint/100067/1/Revision_complete%2520text_clean_LCLT-2014-0299_Methoxphenidine_not%2520for%2520review.pdf | access-date = 2021-05-31 | url-status = live | s2cid = 8513947 | archive-url = https://web.archive.org/web/20210531150825/https://www.zora.uzh.ch/id/eprint/100067/1/Revision_complete%2520text_clean_LCLT-2014-0299_Methoxphenidine_not%2520for%2520review.pdf | archive-date = 2021-05-31 }}{{cite journal | vauthors = Helander A, Beck O, Bäckberg M | title = Intoxications by the dissociative new psychoactive substances diphenidine and methoxphenidine | journal = Clinical Toxicology | volume = 53 | issue = 5 | pages = 446–453 | date = June 2015 | pmid = 25881797 | doi = 10.3109/15563650.2015.1033630 | s2cid = 5962038 }} methoxphenidine has also been associated with three published fatalities{{cite journal | vauthors = Elliott SP, Brandt SD, Wallach J, Morris H, Kavanagh PV | title = First reported fatalities associated with the 'research chemical' 2-methoxydiphenidine | journal = Journal of Analytical Toxicology | volume = 39 | issue = 4 | pages = 287–293 | date = May 2015 | pmid = 25698777 | doi = 10.1093/jat/bkv006 | doi-access = free }} and one case of impaired driving.{{cite journal | vauthors = Stachel N, Jacobsen-Bauer A, Skopp G | title = A methoxydiphenidine-impaired driver | journal = International Journal of Legal Medicine | volume = 130 | issue = 2 | pages = 405–409 | date = March 2016 | pmid = 26482953 | doi = 10.1007/s00414-015-1280-5 | s2cid = 6483817 }}
Psychotic episodes have also been reported, including a murder in June 2014.{{cite web | url=https://www.bbc.com/news/uk-northern-ireland-36556909 | title=Man who killed mother believing her to be a witch sentenced to minimum of five years in jail | publisher=BBC News | date=17 June 2016 | access-date=31 May 2021 | archive-date=24 August 2020 | archive-url=https://web.archive.org/web/20200824165934/https://www.bbc.com/news/uk-northern-ireland-36556909 | url-status=live }}
Legal status
As of October 2015 MXP is a controlled substance in China.{{cite web | url=http://www.sfda.gov.cn/WS01/CL0056/130753.html | title=关于印发《非药用类麻醉药品和精神药品列管办法》的通知 | trans-title = Notice on Issuing the Measures for the Listing and Control of Non-Medicinal Narcotic Drugs and Psychotropic Substances | publisher=China Food and Drug Administration | date=27 September 2015 | language=Chinese | access-date=1 October 2015 | archive-date=1 October 2015 | archive-url=https://web.archive.org/web/20151001222554/http://www.sfda.gov.cn/WS01/CL0056/130753.html | url-status=dead }}
In Canada, MT-45 and its analogues were made Schedule I controlled substances, which includes DPD{{Clarify |date=March 2024}} in its structural group.{{cite journal | vauthors = Arsenault D |date=1 June 2016 |title=Regulations Amending the Food and Drug Regulations (Parts G and J — Lefetamine, AH-7921, MT-45 and W-18) |url=http://www.gazette.gc.ca/rp-pr/p2/2016/2016-06-01/html/sor-dors106-eng.php |url-status=live |journal=Canada Gazette |volume=150 |issue=11 |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 |archive-date=2017-12-02 |access-date=2016-11-17}} Possession without legal authority can result in maximum seven years imprisonment. Further, Health Canada amended the Food and Drug Regulations in May, 2016 to classify explicitly DPD as a restricted drug. Only those with a law enforcement agency, person with an exemption permit or institutions with Minister's authorization may possess the drug.
See also
References
{{Reflist|2}}
{{Hallucinogens}}
{{Ionotropic glutamate receptor modulators}}
{{Phenethylamines}}
Category:NMDA receptor antagonists
Category:1,2-Diarylethylamines