DOTFM

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DOTFM
Clinical data
Other names2,5-Dimethoxy-4-trifluoromethylamphetamine; 4-Trifluoromethyl-2,5-dimethoxyamphetamine; DOTFM; 3C-TFM
Routes of
administration		Oral[1][2]
Legal status
Legal status
Pharmacokinetic data
Duration of actionUnknown[1][2]
Identifiers
  • (RS)-1-[2,5-Dimethoxy-4-(trifluoromethyl)phenyl]propan-2-amine
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC12H16F3NO2
Molar mass263.260 g·mol−1
3D model (JSmol)
  • FC(F)(F)c1cc(OC)c(cc1OC)CC(N)C
  • 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 checkY
  • Key:WPGOTSORDNBMHP-UHFFFAOYSA-N checkY
  (verify)

2,5-Dimethoxy-4-trifluoromethylamphetamine (DOTFM) is a psychedelic drug of the phenethylamine, amphetamine, and DOx families.[3] It is the α-methylated analogue of 2C-TFM. The drug is the most potent DOx psychedelic.[1][2]

Use and effects

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

Interactions

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See also: Psychedelic drug § Interactions, and Trip killer § Serotonergic psychedelic antidotes

Pharmacology

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Pharmacodynamics

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DOTFM acts as an agonist at the serotonin 5-HT2A and 5-HT2C receptors.[3] In drug discrimination tests in rats, DOTFM fully substituted for LSD and was slightly more potent than DOI.[3] In addition, (R)-DOTFM robustly induces the head-twitch response, a behavioral proxy of psychedelic effects, in rodents, with equivalent potency as (R)-DOI.[4] The drug is around twice as potent as 2C-TFM in animal studies.

In contrast to (R)-DOI, which has extraordinarily potent serotonin 5-HT2A receptor-mediated anti-inflammatory effects,[5][6] DOTFM shows no anti-inflammatory effects.[7] The differences between the drugs in this regard appear to be due to differences in functional selectivity at the serotonin 5-HT2A receptor.[7][4]

History

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DOTFM was first synthesized in 1994 by a team at Purdue University led by David E. Nichols.[3] 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.[8][1] Subsequently, Daniel Trachsel described a wider dose range in 2013, although did not report its duration.[2]

See also

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References

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  1. ^ a b c d e f 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. ^ a b c d e f 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. ^ a b c d 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.
  4. ^ a b 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.
  5. ^ 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.
  6. ^ 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.
  7. ^ a b 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.
  8. ^ 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).
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