# DOTFM

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> Markdown URL: https://mediated.wiki/source/DOTFM.md
> Source: https://en.wikipedia.org/wiki/DOTFM
> Source revision: 1342833338
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{{Short description|Psychedelic drug}}
{{for|the internet domain|.fm}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Drugbox
| Verifiedfields = verified
| Watchedfields = verified
| verifiedrevid = 477211798
| drug_name = DOTFM
| image = DOTFM.svg
| image_class = skin-invert-image
| width = 225px

<!-- Clinical data -->
| tradename = 
| pregnancy_category = 
| routes_of_administration = [Oral](/source/Oral_administration)<ref name="Trachsel_2012" /><ref name="Trachsel_2013" />
| class = 

<!-- Legal status -->
| legal_CA = Schedule I
| legal_UK = Class A
| legal_status =

<!-- Pharmacokinetic data -->
| bioavailability = 
| protein_bound = 
| metabolism = 
| onset = 
| elimination_half-life = 
| duration_of_action = Unknown<ref name="Trachsel_2012" /><ref name="Trachsel_2013" />
| excretion =

<!-- Identifiers -->
| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 159277-07-3
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = NLH3FWZ9T4
| CAS_supplemental = <br /> {{CAS|159277-12-0}} (hydrochloride) 
| ATC_prefix = 
| ATC_suffix = 
| PubChem = 10400521
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = 
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 8575959
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 6620
| synonyms = 2,5-Dimethoxy-4-trifluoromethylamphetamine; 4-Trifluoromethyl-2,5-dimethoxyamphetamine; DOTFM; 3C-TFM

<!-- Chemical data -->
| IUPAC_name = (''RS'')-1-[2,5-Dimethoxy-4-(trifluoromethyl)phenyl]propan-2-amine
| C=12 | H=16 | F=3 | N=1 | O=2
| SMILES = FC(F)(F)c1cc(OC)c(cc1OC)CC(N)C
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C12H16F3NO2/c1-7(16)4-8-5-11(18-3)9(12(13,14)15)6-10(8)17-2/h5-7H,4,16H2,1-3H3
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = WPGOTSORDNBMHP-UHFFFAOYSA-N
}}

'''DOTFM''', also known as '''2,5-dimethoxy-4-trifluoromethylamphetamine''', is a [psychedelic drug](/source/psychedelic_drug) of the [phenethylamine](/source/substituted_phenethylamine), [amphetamine](/source/substituted_amphetamine), and [DOx](/source/DOx) families related to [DOM](/source/DOM_(drug)).<ref name="Shulgin_2011" /><ref name="Trachsel_2012" /><ref name="Trachsel_2013" /><ref name="Nichols_1994" /> It is the [α](/source/alpha_carbon)-[methyl](/source/methyl)ated [analogue](/source/structural_analog) of [2C-TFM](/source/2C-TFM).<ref name="Shulgin_2011" /><ref name="Trachsel_2013" /> The drug is the most [potent](/source/potency_(pharmacology)) known DOx psychedelic.<ref name="Trachsel_2012" /><ref name="Trachsel_2013" />

==Use and effects==
According to [Daniel Trachsel](/source/Daniel_Trachsel), DOTFM is active as a psychedelic in humans at doses of 0.3 to 1{{nbsp}}mg (300–1,000{{nbsp}}μg) [orally](/source/oral_administration) and its [duration](/source/duration_of_action) is not listed.<ref name="Trachsel_2012">{{cite journal | vauthors = Trachsel D | title = Fluorine in psychedelic phenethylamines | journal = Drug Test Anal | volume = 4 | issue = 7–8 | pages = 577–590 | date = 2012 | pmid = 22374819 | doi = 10.1002/dta.413 | url = https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=c7b41be36b1f580a264a752521d151e6e2d9409d | url-access = subscription | quote = The 4-trifluoromethyl derivative 2C-TFM (34) was identified as a potent 5-HT2A/C receptor agonist by Nichols et al. in 1994.[28] Together with its a-methyl congener DOTFM (35) it is among the most potent simple phenethylamines at these binding sites, showing comparable or slightly higher binding affinities than DOB (29) and DOI (30).[28] Compared to DOB (29) and DOI (30), both compounds 34 and 35 turned out to be of equal, or slightly increased potency in DD studies (rats, training drug: LSD).[28] Within the context of a DD study, this was the first time for a 2C derivative to be found equally potent to the potent 3C derivatives DOB (29) and DOI (30). In humans, initial experiments seem to be consistent with high potencies (34: 3–5 mg; 35: 0.3 mg or more. A.T. Shulgin, personal communication in 2003).[4] }}</ref><ref name="Trachsel_2013">{{cite book | vauthors = Trachsel D, Lehmann D, Enzensperger C | title = Phenethylamine: von der Struktur zur Funktion | location = Solothurn | year = 2013 | trans-title = Phenethylamines: From Structure to Function | edition = 1 | publisher = Nachtschatten-Verlag | series = Nachtschatten-Science | isbn = 978-3-03788-700-4 | oclc = 858805226 | url = https://books.google.com/books?id=-Us1kgEACAAJ | language = de }}</ref> It is the most [potent](/source/potency_(pharmacology)) psychedelic of the DOx family, followed by [DOB](/source/DOB_(drug)), which has a dose range of 1 to 3{{nbsp}}mg orally.<ref name="Trachsel_2012" /><ref name="Trachsel_2013" />

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

==Pharmacology==
===Pharmacodynamics===
DOTFM acts as an [agonist](/source/agonist) at the [serotonin](/source/serotonin) [5-HT<sub>2A</sub>](/source/5-HT2A_receptor) and [5-HT<sub>2C</sub>](/source/5-HT2C_receptor) [receptor](/source/receptor_(biochemistry))s.<ref name="Nichols_1994" /> In [drug discrimination](/source/drug_discrimination) tests in rats, DOTFM fully substituted for [LSD](/source/LSD) and was slightly more [potent](/source/potency_(pharmacology)) than [DOI](/source/2%2C5-Dimethoxy-4-iodoamphetamine).<ref name="Nichols_1994" /> In addition, (''R'')-DOTFM robustly induces the [head-twitch response](/source/head-twitch_response), a behavioral proxy of psychedelic effects, in rodents, with equivalent potency as (''R'')-DOI.<ref name="Flanagan_2024" /> The drug is around twice as potent as 2C-TFM in [animal studies](/source/animal_study).

In contrast to (''R'')-DOI, which has extraordinarily potent serotonin 5-HT<sub>2A</sub> receptor-mediated [anti-inflammatory](/source/anti-inflammatory) effects,<ref name="Nichols_2017">{{cite journal | vauthors = Nichols DE, Johnson MW, Nichols CD | title = Psychedelics as Medicines: An Emerging New Paradigm | journal = Clinical Pharmacology and Therapeutics | volume = 101 | issue = 2 | pages = 209–219 | date = February 2017 | pmid = 28019026 | doi = 10.1002/cpt.557 }}</ref><ref name="Yu_2008">{{cite journal | vauthors = Yu B, Becnel J, Zerfaoui M, Rohatgi R, Boulares AH, Nichols CD | title = Serotonin 5-hydroxytryptamine(2A) receptor activation suppresses tumor necrosis factor-alpha-induced inflammation with extraordinary potency | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 327 | issue = 2 | pages = 316–323 | date = November 2008 | pmid = 18708586 | doi = 10.1124/jpet.108.143461 }}</ref> DOTFM shows no anti-inflammatory effects.<ref name="Flanagan_2022">{{cite journal | vauthors = Flanagan TW, Billac G, Nichols CD | title = Differential Regulation of Inflammatory Responses Following 5-HT 2 Receptor Activation in Pulmonary Tissues | journal = The FASEB Journal | volume = 36 | issue = S1 | date = 2022 | doi = 10.1096/fasebj.2022.36.S1.R2617 | issn = 0892-6638 | article-number = fasebj.2022.36.S1.R2617 | doi-access = free }}</ref> The differences between the drugs in this regard appear to be due to differences in [functional selectivity](/source/functional_selectivity) at the serotonin 5-HT<sub>2A</sub> receptor.<ref name="Flanagan_2022" /><ref name="Flanagan_2024">{{cite journal | vauthors = Flanagan TW, Foster TP, Galbato TE, Lum PY, Louie B, Song G, Halberstadt AL, Billac GB, Nichols CD | title = Serotonin-2 Receptor Agonists Produce Anti-inflammatory Effects through Functionally Selective Mechanisms That Involve the Suppression of Disease-Induced Arginase 1 Expression | journal = ACS Pharmacology & Translational Science | volume = 7 | issue = 2 | pages = 478–492 | date = February 2024 | pmid = 38357283 | pmc = 10863441 | doi = 10.1021/acsptsci.3c00297 | quote = The effects of (R)-DOTFM were examined in the head-twitch response (HTR) assay. (R)-DOTFM produced a strong HTR with a potent ED 50 of 0.60 μmol/kg. These values are equivalent to (R)-DOI, as previously determined. }}</ref>

==Chemistry==
===Synthesis===
The [chemical synthesis](/source/chemical_synthesis) of DOTFM has been described.<ref name="Shulgin_2011" /><ref name="Nichols_1994" />

===Analogues===
[Analogue](/source/Structural_analog)s of DOTFM include [2C-TFM](/source/2C-TFM), [4C-TFM](/source/4C-TFM) (TFM-Ariadne; 4C-DOTFM), [DOTFE](/source/DOTFE), [TFMFly](/source/TFMFly) (DOTFM-FLY), and [25TFM-NBOMe](/source/25TFM-NBOMe), among others.

==History==
DOTFM was first [synthesized](/source/chemical_synthesis) in 1994 by a team at [Purdue University](/source/Purdue_University) led by [David E. Nichols](/source/David_E._Nichols).<ref name="Nichols_1994">{{cite journal | vauthors = Nichols DE, Frescas S, Marona-Lewicka D, Huang X, Roth BL, Gudelsky GA, Nash JF | title = 1-(2,5-Dimethoxy-4-(trifluoromethyl)phenyl)-2-aminopropane: a potent serotonin 5-HT2A/2C agonist | journal = Journal of Medicinal Chemistry | volume = 37 | issue = 25 | pages = 4346–4351 | date = December 1994 | pmid = 7996545 | doi = 10.1021/jm00051a011 | author5-link = Bryan Roth }}</ref> The threshold dose in humans was reported by [Alexander Shulgin](/source/Alexander_Shulgin) in his 2011 book ''[The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds](/source/The_Shulgin_Index%2C_Volume_One%3A_Psychedelic_Phenethylamines_and_Related_Compounds)'', who cited personal communication with an anonymous individual in 2003 as the source for the information.<ref name="Shulgin_2011">{{cite book | vauthors = Shulgin A, Manning T, Daley P | title = [The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds](/source/The_Shulgin_Index%2C_Volume_One%3A_Psychedelic_Phenethylamines_and_Related_Compounds) | location = Berkeley | volume = 1 | year = 2011 | publisher = [Transform Press](/source/Transform_Press) | isbn = 978-0-9630096-3-0 | quote = Threshold oral activity [of DOTFM] reported in humans at 300 µg (Anon., 2003). }}</ref><ref name="Trachsel_2012" /> Subsequently, [Daniel Trachsel](/source/Daniel_Trachsel) described a wider dose range in 2013, although did not report its [duration](/source/duration_of_action).<ref name="Trachsel_2013" />

==Society and culture==
===Legal status===
====Canada====
DOTFM is a [controlled substance](/source/controlled_substance) in [Canada](/source/Canada) under phenethylamine blanket-ban language.<ref name="CDSA">{{cite web | title=Controlled Drugs and Substances Act | website=Department of Justice Canada | url=https://laws-lois.justice.gc.ca/eng/acts/c-38.8/FullText.html | access-date=19 January 2026}}</ref>

==See also==
* [DOx (psychedelics)](/source/DOx_(psychedelics))
* [2C-iBu](/source/2C-iBu) (ELE-02)
* [5-HT<sub>2A</sub> receptor § Anti-inflammatory effects](/source/5-HT2A_receptor)

== References ==
{{Reflist}}

==External links==
* [https://isomerdesign.com/pihkal/explore/5381 DOTFM - Isomer Design]
* [https://archive.org/details/shulgin-index-vol-1/page/133/mode/1up DOTFM - The Shulgin Index]

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

{{DEFAULTSORT:Dimethoxy-4-trifluoromethylamphetamine, 2,5-}}

Category:5-HT2A agonists
Category:5-HT2C agonists
Category:Daniel Trachsel
Category:David E. Nichols
Category:DOx (psychedelics)
Category:Psychedelic phenethylamines
Category:Substances discovered in the 1990s
Category:Trifluoromethyl compounds

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Adapted from the Wikipedia article [DOTFM](https://en.wikipedia.org/wiki/DOTFM) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/DOTFM?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.