Chemistry:DOTFM

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

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) and its duration is not listed.[2][3] It is the most potent psychedelic of the DOx family, followed by DOB (dose range 1–3 mg).[2][3]

Interactions

Pharmacology

Pharmacodynamics

DOTFM acts as an agonist at the serotonin 5-HT2A and 5-HT2C receptors.[1] In drug discrimination tests in rats, DOTFM fully substituted for LSD and was slightly more potent than DOI.[1] 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

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

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 "1-(2,5-Dimethoxy-4-(trifluoromethyl)phenyl)-2-aminopropane: a potent serotonin 5-HT2A/2C agonist". Journal of Medicinal Chemistry 37 (25): 4346–4351. December 1994. doi:10.1021/jm00051a011. PMID 7996545. 
  2. ↑ 2.0 2.1 2.2 2.3 "Fluorine in psychedelic phenethylamines". Drug Test Anal 4 (7–8): 577–590. 2012. doi:10.1002/dta.413. PMID 22374819. https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=c7b41be36b1f580a264a752521d151e6e2d9409d. "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]". 
  3. ↑ 3.0 3.1 3.2 3.3 (in de) Phenethylamine: von der Struktur zur Funktion. Nachtschatten-Science (1 ed.). Solothurn: Nachtschatten-Verlag. 2013. ISBN 978-3-03788-700-4. OCLC 858805226. https://books.google.com/books?id=-Us1kgEACAAJ. 
  4. ↑ 4.0 4.1 "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. February 2024. doi:10.1021/acsptsci.3c00297. 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. ↑ "Psychedelics as Medicines: An Emerging New Paradigm". Clinical Pharmacology and Therapeutics 101 (2): 209–219. February 2017. doi:10.1002/cpt.557. PMID 28019026. 
  6. ↑ "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. November 2008. doi:10.1124/jpet.108.143461. PMID 18708586. 
  7. ↑ 7.0 7.1 "Differential Regulation of Inflammatory Responses Following 5-HT 2 Receptor Activation in Pulmonary Tissues". The FASEB Journal 36 (S1). 2022. doi:10.1096/fasebj.2022.36.S1.R2617. ISSN 0892-6638. 
  8. ↑ The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds. 1. Berkeley: Transform Press. 2011. ISBN 978-0-9630096-3-0. "Threshold oral activity [of DOTFM] reported in humans at 300 µg (Anon., 2003)." 

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