View source for Escaline

{{Short description|Psychedelic phenthylamine drug}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox drug
| Verifiedfields = verified
| Watchedfields = verified
| verifiedrevid = 408945247
| drug_name = 
| image = Escaline2DACS.svg
| image_class = skin-invert-image
| width = 225px
| image2 = Escaline-3d-sticks.png
| image_class2 = bg-transparent
| width2 = 225px

<!-- Clinical data -->
| pronounce = 
| tradename = 
| Drugs.com = 
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| licence_EU = 
| DailyMedID = 
| licence_US = 
| pregnancy_AU = 
| pregnancy_category = 
| dependency_liability = 
| addiction_liability = 
| routes_of_administration = [[Oral administration|Oral]]<ref name="PiHKAL" />
| class = [[Serotonin receptor modulator]]; [[Serotonergic psychedelic]]; [[Hallucinogen]]
| ATC_prefix = None
| ATC_suffix = 

<!-- Legal status -->
| legal_status = 

<!-- Pharmacokinetic data -->
| bioavailability = 
| protein_bound = 
| metabolism = 
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| onset = 
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| duration_of_action = 8–12 hours<ref name="PiHKAL" />
| excretion = 

<!-- Identifiers -->
| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 39201-82-6
| CAS_supplemental = 
| PubChem = 38240
| PubChemSubstance = 
| IUPHAR_ligand = 
| DrugBank = 
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 35053
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = Q13F1C1N8I
| KEGG = 
| ChEBI = 
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 319415
| NIAID_ChemDB = 
| PDB_ligand = 
| 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" />

==Use and effects==
In his book ''[[PiHKAL|PiHKAL]]'' (''Phenethylamines I Have Known and Loved''), [[Alexander Shulgin]] lists the dose range of escaline 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|duration]] is stated to be 8 to 12{{nbsp}}hours, whereas the [[onset of action|onset]] is not described.<ref name="PiHKAL" /> Escaline is approximately 5- to 8-fold more [[potency (pharmacology)|potent]] than mescaline.<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>

The effects of escaline have been described relatively limitedly but have been reported to include [[sense|sensory]] enhancement without an intellectual component, little synthesis of external sensory inputs like [[music]] or [[visual perception|visual]] [[stimulus (psychology)|stimuli]], easy [[fantasy (psychology)|fantasy]], [[rational thinking]] and [[insight]], pleasantness, powerful and complex [[drug intoxication|intoxication]], [[analgesia|pain relief]], [[muscle tension]], [[motor incoordination]] to the extent of not being able to walk or tie one's shoelaces, body tension that outweighed the desired psychoactive effects, [[tachycardia]], [[dehydration]], [[nightmare]]s, and next-day [[hangover]] symptoms such as [[tiredness]] and low [[mental energy|energy]].<ref name="PiHKAL" />

==Interactions==
{{See also|Psychedelic drug#Interactions|Trip killer#Serotonergic psychedelic antidotes}}

==Pharmacology==
===Pharmacodynamics===
The [[receptor (biochemistry)|receptor]] interactions of escaline and [[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 =  | article-number = 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><ref name="JainGumpperSlocum2025">{{cite journal | vauthors = Jain MK, Gumpper RH, Slocum ST, Schmitz GP, Madsen JS, Tummino TA, Suomivuori CM, Huang XP, Shub L, DiBerto JF, Kim K, DeLeon C, Krumm BE, Fay JF, Keiser M, Hauser AS, Dror RO, Shoichet B, Gloriam DE, Nichols DE, Roth BL | title = The polypharmacology of psychedelics reveals multiple targets for potential therapeutics | journal = Neuron | volume = | issue = | pages = | date = July 2025 | pmid = 40683247 | doi = 10.1016/j.neuron.2025.06.012 | url = https://web.archive.org/web/20250725061718/https://www.cell.com/cms/10.1016/j.neuron.2025.06.012/attachment/7d8365fe-51f3-4a28-bf40-9999bec837f6/mmc11.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 =  | article-number = 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>

==Society and culture==
===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 [[3,4,5-trimethoxyamphetamine]] (TMA).<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]
* [https://isomerdesign.com/countyourculture/2012/05/04/leminger-allylescaline/ Leminger's Scalines - countyourculture]

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

[[Category:5-HT2A agonists]]
[[Category:5-HT2B agonists]]
[[Category:5-HT2C agonists]]
[[Category:David E. Nichols]]
[[Category:Designer drugs]]
[[Category:Ethoxy compounds]]
[[Category:O-methylated phenols]]
[[Category:Phenol ethers]]
[[Category:Psychedelic phenethylamines]]
[[Category:Scalines]]