Editing Escaline

{{Short description|Psychedelic phenthylamine drug}}
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{{Infobox drug
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| verifiedrevid = 408945247
| drug_name = 
| image = Escaline2DACS.svg
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| image2 = Escaline-3d-sticks.png
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| routes_of_administration = [[Oral administration|Oral]]<ref name="PiHKAL" />
| class = [[Serotonergic psychedelic]]; [[Hallucinogen]]
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<!-- Pharmacokinetic data -->
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| duration_of_action = 8–12 hours<ref name="PiHKAL" />
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<!-- Identifiers -->
| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 39201-82-6
| CAS_supplemental = 
| PubChem = 38240
| PubChemSubstance = 
| IUPHAR_ligand = 
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 35053
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = Q13F1C1N8I
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| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 319415
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| synonyms = E; 3,5-Dimethoxy-4-ethoxyphenethylamine; 4-Ethoxy-3,5-dimethoxyphenethylamine

<!-- Chemical data -->
| IUPAC_name = 2-(4-ethoxy-3,5-dimethoxyphenyl)ethan-1-amine
| C=12 | H=19 | N=1 | O=3
| SMILES = NCCC1=CC(OC)=C(OCC)C(OC)=C1
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C12H19NO3/c1-4-16-12-10(14-2)7-9(5-6-13)8-11(12)15-3/h7-8H,4-6,13H2,1-3H3
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = RHOGRSKNWDNCDN-UHFFFAOYSA-N

<!-- Physical data -->
| melting_point = 165
| melting_high = 166
| melting_notes = ([[hydrochloride]])
}}

'''Escaline''' ('''E'''), also known as '''3,5-dimethoxy-4-ethoxyphenethylamine''', is a [[psychedelic drug]] of the [[substituted phenethylamine|phenethylamine]] and [[substituted mescaline analogue|scaline]] families related to [[mescaline]].<ref name="PiHKAL" /> It is the 4-[[ethoxy group|ethoxy]] [[structural analogue|analogue]] of mescaline (3,4,5-trimethoxyphenethylamine) and the phenethylamine (non-α-methyl) analogue of [[3C-E]] (3,5-dimethoxy-4-ethoxyamphetamine).<ref name="PiHKAL" />

==Effects==
The effects of escaline and related [[mescaline]] analogues in humans were first described by [[Alexander Shulgin]].<ref name="PiHKAL" /> In his book ''[[PiHKAL|PiHKAL (Phenethylamines i Have Known And Loved)]]'', Shulgin lists the dosage range as 40 to 60{{nbsp}}mg of the [[hydrochloride]] [[salt (chemistry)|salt]] taken [[oral administration|orally]].<ref name="PiHKAL">{{Cite web|url=https://www.erowid.org/library/books_online/pihkal/pihkal072.shtml|title=Erowid Online Books : "PIHKAL" - #72 E| website=www.erowid.org|access-date=2024-02-02|archive-date=2023-05-06|archive-url= https://web.archive.org/web/20230506192807/https://www.erowid.org/library/books_online/pihkal/pihkal072.shtml|url-status=live}}</ref><ref name="HalberstadtChathaKlein2020" /> The duration of action was stated to be 8 to 12{{nbsp}}hours.<ref name="PiHKAL" /> Escaline is approximately 5- to 8-fold more [[potency (pharmacology)|potent]] than mescaline in humans.<ref name="BlaazerSmidKruse2008">{{cite journal | vauthors = Blaazer AR, Smid P, Kruse CG | title = Structure-activity relationships of phenylalkylamines as agonist ligands for 5-HT(2A) receptors | journal = ChemMedChem | volume = 3 | issue = 9 | pages = 1299–1309 | date = September 2008 | pmid = 18666267 | doi = 10.1002/cmdc.200800133 | url = https://www.thevespiary.org/rhodium/Rhodium/Vespiary/talk/files/1981-Structure%E2%80%93Activity-Relationships-of-Phenylalkylamines-asAgonist-Ligands-for-5-HT2A-Receptors807f.pdf | archive-url = https://web.archive.org/web/20190721062032/https://www.thevespiary.org/rhodium/Rhodium/Vespiary/talk/files/1981-Structure%E2%80%93Activity-Relationships-of-Phenylalkylamines-asAgonist-Ligands-for-5-HT2A-Receptors807f.pdf | archive-date = 21 July 2019 }}</ref>

==Pharmacology==
The [[receptor (biochemistry)|receptor]] interactions of escaline [[structural analogue|analogue]]s have been described.<ref name="KolaczynskaLuethiTrachsel2021">{{cite journal | vauthors = Kolaczynska KE, Luethi D, Trachsel D, Hoener MC, Liechti ME | title = Receptor Interaction Profiles of 4-Alkoxy-3,5-Dimethoxy-Phenethylamines (Mescaline Derivatives) and Related Amphetamines | journal = Frontiers in Pharmacology | volume = 12 | issue =  | pages = 794254 | date = 2021 | pmid = 35222010 | pmc = 8865417 | doi = 10.3389/fphar.2021.794254 | doi-access = free | url = https://edoc.unibas.ch/87985/1/fphar-12-794254.pdf }}</ref>

Escaline produces the [[head-twitch response]], a behavioral proxy of [[psychedelic drug|psychedelic]]-like effects, in rodents.<ref name="HalberstadtChathaChapman2019">{{cite journal | vauthors = Halberstadt AL, Chatha M, Chapman SJ, Brandt SD | title = Comparison of the behavioral effects of mescaline analogs using the head twitch response in mice | journal = Journal of Psychopharmacology | volume = 33 | issue = 3 | pages = 406–414 | date = March 2019 | pmid = 30789291 | pmc = 6848748 | doi = 10.1177/0269881119826610 | url = https://www.researchgate.net/publication/331263972 }}</ref><ref name="HalberstadtChathaKlein2020">{{cite journal | vauthors = Halberstadt AL, Chatha M, Klein AK, Wallach J, Brandt SD | title = Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species | journal = Neuropharmacology | volume = 167 | issue =  | pages = 107933 | date = May 2020 | pmid = 31917152 | pmc = 9191653 | doi = 10.1016/j.neuropharm.2019.107933 | url = http://usdbiology.com/cliff/Courses/Advanced%20Seminars%20in%20Neuroendocrinology/Serotonergic%20Psychedelics%2020/Halberstadt%2020%20Neuropharm%20potency%20of%20hallucinogens%20%20head-twitch.pdf }}</ref> It partially substitutes for [[LSD]] in rodent [[drug discrimination]] tests.<ref name="CasselsSáez-Briones2018">{{cite journal | vauthors = Cassels BK, Sáez-Briones P | title = Dark Classics in Chemical Neuroscience: Mescaline | journal = ACS Chemical Neuroscience | volume = 9 | issue = 10 | pages = 2448–2458 | date = October 2018 | pmid = 29847089 | doi = 10.1021/acschemneuro.8b00215 | url = https://shaunlacob.com/wp-content/uploads/2020/12/DC-MESCALINE.pdf | quote = In the case of the 3,4,5- trioxygenated compounds, binding studies at 5-HT2A and 5- HT2C receptors revealed somewhat higher affinities than mescaline but, in phosphoinositide hydrolysis assays (only for 5-HT2A), lower efficacies relative to serotonin and the full agonist mescaline (60 and 45%, respectively). More striking, however, was the observation that the new compounds did not fully substitute for LSD in LSD-trained rats, and at doses well above the mescaline EC50, only 50 and 29% appropriate responding was recorded. In view of this unexpected result, 3,5- dimethoxy-4-ethoxyphenethylamine (escaline), which is considerably more potent than mescaline in humans,128 was also tested. It was found to have about twice the affinity of mescaline for 5-HT2A receptors and was a complete agonist with very similar functional potency, but again it failed to substitute completely for LSD in the drug discrimination experiments. }}</ref>

==History==
Escaline was first [[chemical synthesis|synthesized]] and reported in the [[scientific literature]] by Benington and colleagues in 1954.<ref name="BeningtonMorinClarke1954">{{cite journal | vauthors = Benington F, Morin RD, Clarke LC | title=Synthesis of 4-Hydroxy- and 4-Ethoxy-3,5-dimethoxy-β-phenethylamines 1 | journal=Journal of the American Chemical Society | volume=76 | issue=21 | date=1954 | issn=0002-7863 | doi=10.1021/ja01650a084 | pages=5555–5556| bibcode=1954JAChS..76.5555B }}</ref> It was later re-examined in the laboratory of [[David E. Nichols]], who prepared a series of [[mescaline]] [[structural analog|analogue]]s that included escaline, [[proscaline]], and [[isoproscaline]] and published their work in 1977.<ref name="NicholsDyer1977">{{cite journal | vauthors = Nichols DE, Dyer DC | title = Lipophilicity and serotonin agonist activity in a series of 4-substituted mescaline analogues | journal = Journal of Medicinal Chemistry | volume = 20 | issue = 2 | pages = 299–301 | date = February 1977 | pmid = 836502 | doi = 10.1021/jm00212a022 }}</ref><ref name="NicholsShulginDyer1977">{{cite journal | vauthors = Nichols DE, Shulgin AT, Dyer DC | title = Directional lipophilic character in a series of psychotomimetic phenethylamine derivatives | journal = Life Sciences | volume = 21 | issue = 4 | pages = 569–575 | date = August 1977 | pmid = 904435 | doi = 10.1016/0024-3205(77)90099-6 }}</ref>

==Legal status==
===Sweden===
Escaline is illegal in [[Sweden]] as of 26 January 2016.<ref>{{cite web | url=http://www.folkhalsomyndigheten.se/nyheter-och-press/nyhetsarkiv/2015/november/31-nya-amnen-kan-klassas-som-narkotika-eller-halsofarlig-vara/ | title=31 nya ämnen kan klassas som narkotika eller hälsofarlig vara | publisher=Folkhälsomyndigheten | language=Swedish | date=November 2015 | access-date=2024-02-02 | archive-date=2017-08-05 | archive-url=https://web.archive.org/web/20170805220841/https://www.folkhalsomyndigheten.se/nyheter-och-press/nyhetsarkiv/2015/november/31-nya-amnen-kan-klassas-som-narkotika-eller-halsofarlig-vara/ | url-status=live }}</ref>

===United States===
Escaline is a Schedule I controlled substance (DEA #7930) in the [[United States]] with the reason cited being that it is a [[positional isomer]] of TMA (3,4,5-trimethoxyamphetamine).<ref name="USDOJ">{{cite web| url=https://www.deadiversion.usdoj.gov/schedules/orangebook/c_cs_alpha.pdf| title=Controlled Substances - Alphabetical Order | publisher = U.S. Department of Justice | work = Diversion Control Division, Drug Enforcement Administration | date = December 2024 | access-date=2024-02-02| archive-date=2021-04-21| archive-url=https://web.archive.org/web/20210421180644/https://www.deadiversion.usdoj.gov/schedules/orangebook/c_cs_alpha.pdf| url-status=live}}</ref>

== See also ==
* [[Substituted mescaline analogue]]

== References ==
{{Reflist}}

== External links ==
* [https://isomerdesign.com/pihkal/explore/72 Escaline - Isomer Design]
* [https://psychonautwiki.org/wiki/Escaline Escaline - PsychonautWiki]
* [https://isomerdesign.com/pihkal/explore/72 The Small & Handy Escaline Thread - Bluelight]
* [https://erowid.org/library/books_online/pihkal/pihkal072.shtml Escaline - PiHKAL - Erowid]
* [https://isomerdesign.com/pihkal/read/pk/72 Escaline - PiHKAL - Isomer Design]

{{Psychedelics}}
{{Serotonin receptor modulators}}
{{Phenethylamines}}

[[Category:5-HT2A agonists]]
[[Category:Designer drugs]]
[[Category:Ethoxy compounds]]
[[Category:O-methylated phenols]]
[[Category:Phenol ethers]]
[[Category:Psychedelic phenethylamines]]
[[Category:Scalines]]