DOTFM

Psychedelic drug From Wikipedia, the free encyclopedia

DOTFM, also known as 2,5-dimethoxy-4-trifluoromethylamphetamine, is a psychedelic drug of the phenethylamine, amphetamine, and DOx families related to DOM.^[3]^[1]^[2]^[4] It is the α-methylated analogue of 2C-TFM.^[3]^[2] The drug is the most potent known DOx psychedelic.^[1]^[2]

Other names2,5-Dimethoxy-4-trifluoromethylamphetamine; 4-Trifluoromethyl-2,5-dimethoxyamphetamine; DOTFM; 3C-TFM

Routes of
administrationOral^[1]^[2]

Legal status

CA: Schedule I
UK: Class A

Duration of actionUnknown^[1]^[2]

Quick facts Clinical data, Other names ...

DOTFM
Clinical data

Other names	2,5-Dimethoxy-4-trifluoromethylamphetamine; 4-Trifluoromethyl-2,5-dimethoxyamphetamine; DOTFM; 3C-TFM
Routes of administration	Oral^[1]^[2]
Legal status
Legal status	CA: Schedule I UK: Class A
Pharmacokinetic data
Duration of action	Unknown^[1]^[2]
Identifiers
IUPAC name (RS)-1-[2,5-Dimethoxy-4-(trifluoromethyl)phenyl]propan-2-amine
CAS Number	159277-07-3^Y 159277-12-0 (hydrochloride)
PubChem CID	10400521
ChemSpider	8575959^Y
UNII	NLH3FWZ9T4
ChEMBL	ChEMBL6620^Y
CompTox Dashboard (EPA)	DTXSID40439330
Chemical and physical data
Formula	C₁₂H₁₆F₃NO₂
Molar mass	263.260 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES FC(F)(F)c1cc(OC)c(cc1OC)CC(N)C
InChI InChI=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^Y Key:WPGOTSORDNBMHP-UHFFFAOYSA-N^Y
(verify)

Use and effects

According to Daniel Trachsel, DOTFM is active as a psychedelic in humans at doses of 0.3 to 1 mg (300–1,000 μg) orally and its duration is not listed.^[1]^[2] It is the most potent psychedelic of the DOx family, followed by DOB, which has a dose range of 1 to 3 mg orally.^[1]^[2]

Interactions

Pharmacology

Pharmacodynamics

DOTFM acts as an agonist at the serotonin 5-HT_2A and 5-HT_2C receptors.^[4] In drug discrimination tests in rats, DOTFM fully substituted for LSD and was slightly more potent than DOI.^[4] In addition, (R)-DOTFM robustly induces the head-twitch response, a behavioral proxy of psychedelic effects, in rodents, with equivalent potency as (R)-DOI.^[5] The drug is around twice as potent as 2C-TFM in animal studies.

In contrast to (R)-DOI, which has extraordinarily potent serotonin 5-HT_2A receptor-mediated anti-inflammatory effects,^[6]^[7] DOTFM shows no anti-inflammatory effects.^[8] The differences between the drugs in this regard appear to be due to differences in functional selectivity at the serotonin 5-HT_2A receptor.^[8]^[5]

Chemistry

Synthesis

The chemical synthesis of DOTFM has been described.^[3]^[4]

Analogues

Analogues of DOTFM include 2C-TFM, 4C-TFM (TFM-Ariadne; 4C-DOTFM), DOTFE, TFMFly (DOTFM-FLY), and 25TFM-NBOMe, among others.

History

DOTFM was first synthesized in 1994 by a team at Purdue University led by David E. Nichols.^[4] The threshold dose in humans was reported by Alexander Shulgin in his 2011 book The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds, who cited personal communication with an anonymous individual in 2003 as the source for the information.^[3]^[1] Subsequently, Daniel Trachsel described a wider dose range in 2013, although did not report its duration.^[2]

Society and culture

Legal status

Canada

DOTFM is a controlled substance in Canada under phenethylamine blanket-ban language.^[9]

References

[1]
Trachsel D (2012). "Fluorine in psychedelic phenethylamines". Drug Test Anal. 4 (7–8): 577–590. doi:10.1002/dta.413. PMID 22374819. 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]
[2]
Trachsel D, Lehmann D, Enzensperger C (2013). Phenethylamine: von der Struktur zur Funktion [Phenethylamines: From Structure to Function]. Nachtschatten-Science (in German) (1 ed.). Solothurn: Nachtschatten-Verlag. ISBN 978-3-03788-700-4. OCLC 858805226.
[3]
Shulgin A, Manning T, Daley P (2011). The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds. Vol. 1. Berkeley: Transform Press. ISBN 978-0-9630096-3-0. Threshold oral activity [of DOTFM] reported in humans at 300 µg (Anon., 2003).
[4]
Nichols DE, Frescas S, Marona-Lewicka D, Huang X, Roth BL, Gudelsky GA, et al. (December 1994). "1-(2,5-Dimethoxy-4-(trifluoromethyl)phenyl)-2-aminopropane: a potent serotonin 5-HT2A/2C agonist". Journal of Medicinal Chemistry. 37 (25): 4346–4351. doi:10.1021/jm00051a011. PMID 7996545.
[5]
Flanagan TW, Foster TP, Galbato TE, Lum PY, Louie B, Song G, et al. (February 2024). "Serotonin-2 Receptor Agonists Produce Anti-inflammatory Effects through Functionally Selective Mechanisms That Involve the Suppression of Disease-Induced Arginase 1 Expression". ACS Pharmacology & Translational Science. 7 (2): 478–492. doi:10.1021/acsptsci.3c00297. PMC 10863441. PMID 38357283. 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.
[6]
Nichols DE, Johnson MW, Nichols CD (February 2017). "Psychedelics as Medicines: An Emerging New Paradigm". Clinical Pharmacology and Therapeutics. 101 (2): 209–219. doi:10.1002/cpt.557. PMID 28019026.
[7]
Yu B, Becnel J, Zerfaoui M, Rohatgi R, Boulares AH, Nichols CD (November 2008). "Serotonin 5-hydroxytryptamine(2A) receptor activation suppresses tumor necrosis factor-alpha-induced inflammation with extraordinary potency". The Journal of Pharmacology and Experimental Therapeutics. 327 (2): 316–323. doi:10.1124/jpet.108.143461. PMID 18708586.
[8]
Flanagan TW, Billac G, Nichols CD (2022). "Differential Regulation of Inflammatory Responses Following 5-HT 2 Receptor Activation in Pulmonary Tissues". The FASEB Journal. 36 (S1) fasebj.2022.36.S1.R2617. doi:10.1096/fasebj.2022.36.S1.R2617. ISSN 0892-6638.
[9]
"Controlled Drugs and Substances Act". Department of Justice Canada. Retrieved 19 January 2026.

DOTFM

Use and effects

Interactions

Pharmacology

Pharmacodynamics

Chemistry

Synthesis

Analogues

History

Society and culture

Legal status

Canada

See also

References

External links

Related Articles