2,5-Dimethoxy-4-fluoroamphetamine

DOF
Clinical data
Other namesDOF; 2,5-Dimethoxy-4-fluoroamphetamine; 4-Fluoro-2,5-dimethoxyamphetamine
Routes of
administration		Oral
Drug classSerotonin receptor modulator; Serotonin 5-HT2A receptor agonist; Stimulant; Possible psychedelic drug
ATC code
  • None
Legal status
Legal status
Identifiers
  • 1-(4-fluoro-2,5-dimethoxyphenyl)propan-2-amine
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC11H16FNO2
Molar mass213.252 g·mol−1
3D model (JSmol)
  • CC(CC1=CC(=C(C=C1OC)F)OC)N
  • InChI=1S/C11H16FNO2/c1-7(13)4-8-5-11(15-3)9(12)6-10(8)14-2/h5-7H,4,13H2,1-3H3 checkY
  • Key:NRANUECGGQVXOT-UHFFFAOYSA-N checkY
  (verify)

2,5-Dimethoxy-4-fluoroamphetamine (DOF) is a serotonin receptor modulator and possible psychedelic drug of the phenethylamine, amphetamine, and DOx families. It is taken orally. The drug was encountered as a novel designer drug in Europe in 2015.

Use and effects

In his books PiHKAL (Phenethylamines I Have Known and Loved) and The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds, Alexander Shulgin states that the properties and effects of DOF in humans are unknown. Based on animal studies however, specifically drug discrimination tests, he estimates that it would be 4- to 6-fold less potent than DOI and DOB as a psychedelic drug in humans. In his more book Phenethylamine: von der Struktur zur Funktion and other publications, Daniel Trachsel lists the dose of DOF as 10 mg or more orally. He states that DOF produces stimulating effects at a dose of 6 mg three times each spaced by 1 hour (18 mg total) orally based on initial anecdotal findings.

Interactions

Pharmacology

Pharmacodynamics

The receptor and transporter interactions of DOF have been characterized. As with other DOx drugs, it shows affinity for the serotonin 5-HT2 receptors and acts as a partial to full agonist of the serotonin 5-HT2A and 5-HT2B receptors. However, it shows much lower affinity for the serotonin 5-HT2 receptors than many other DOx drugs and a much lower degree of selectivity for the serotonin 5-HT2A receptor over the serotonin 5-HT1A receptor. On the other hand, the activational potencies of DOF at the serotonin 5-HT2A and 5-HT2B receptors were similar to those of DOB. The drug lacks significant affinity for the monoamine transporters (MATs), the human trace amine-associated receptor 1 (TAAR1), and various other receptors.

DOF substituted for DOM in rodent drug discrimination tests, albeit with 4- to 6-fold lower potency than other DOx drugs like DOI and DOB.

Daniel Trachsel further suspected that the molar refraction of the important 4-substituent in DOF and 2C-F may be too low to activate the serotonin 5-HT2A receptor sufficiently to produce psychedelic effects. DOF more closely mimics the effects of the 4-unsubstituted 2,5-dimethoxyamphetamine than the effects of DOC, DOB, and DOI.

Chemistry

Synthesis

The chemical synthesis of DOF has been described.

Analogues

Analogues of DOF include DOI, DOB, DOC, DOTFM, 2C-F, and 25F-NBOMe, among others.

History

DOF was first described in the scientific literature by Richard Glennon and colleagues by 1982. Subsequently, its properties and effects in humans were described by Daniel Trachsel in 2012. The drug was encountered as a novel designer drug in Slovenia in 2015.

Society and culture

Canada

DOF is a controlled substance in Canada under phenethylamine blanket-ban language.

United States

DOF is not an explicitly controlled substance in the United States. However, it could be considered a Schedule I controlled substance as an analogue of DOM and DOB under the Federal Analogue Act in this country.

See also

References

  1. 1 2 3 4 5 6 7 8 9 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. Archived from the original on 21 August 2025.
  2. 1 2 3 4 5 6 7 8 9 Trachsel D (July 2012). "Fluorine in psychedelic phenethylamines". Drug Testing and Analysis. 4 (7–8): 577–590. doi:10.1002/dta.413. PMID 22374819.
  3. 1 2 3 4 5 6 Shulgin A, Shulgin A (September 1991). PiHKAL: A Chemical Love Story. Berkeley, California: Transform Press. ISBN 0-9630096-0-5. OCLC 25627628. "The three-carbon amphetamine analogue of 2C-F would quite logically be called DOF (2,5-dimethoxy-4-fluoroamphetamine). It has been prepared by reaction of the above benzaldehyde with nitroethane (giving 1-(2,5-dimethoxy-4-fluorophenyl)-2-nitropropene, with a melting point of 128–129 °C from ethanol) followed by LAH reduction to DOF (the hydrochloride salt has a melting point of 166–167 °C, after recrystallization from ether/ethyl acetate/ethanol). Animal studies that have compared DOF to the highly potent DOI and DOB imply that the human activity will be some four to six times less than these two heavier halide analogues. As of the present time, no human trials of DOF have been made."
  4. 1 2 3 4 5 6 7 8 Shulgin A, Manning T, Daley PF (2011). The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds. Vol. 1. Berkeley: Transform Press. ISBN 978-0-9630096-3-0.
  5. 1 2 "EMCDDA2016". isomerdesign.com.
  6. 1 2 3 Glennon RA, Young R, Benington F, Morin RD (October 1982). "Behavioral and serotonin receptor properties of 4-substituted derivatives of the hallucinogen 1-(2,5-dimethoxyphenyl)-2-aminopropane". Journal of Medicinal Chemistry. 25 (10): 1163–1168. doi:10.1021/jm00352a013. PMID 7143352.
  7. 1 2 3 Shannon M, Battaglia G, Glennon RA, Titeler M (June 1984). "5-HT1 and 5-HT2 binding properties of derivatives of the hallucinogen 1-(2,5-dimethoxyphenyl)-2-aminopropane (2,5-DMA)". European Journal of Pharmacology. 102 (1): 23–29. doi:10.1016/0014-2999(84)90333-9. PMID 6479216.
  8. 1 2 3 Glennon RA (January 1987). "Central serotonin receptors as targets for drug research". Journal of Medicinal Chemistry. 30 (1): 1–12. doi:10.1021/jm00384a001. PMID 3543362. Table II. Affinities of Selected Phenalkylamines for 5-HT1 and 5-HT2 Binding Sites
  9. 1 2 3 Nelson DL, Lucaites VL, Wainscott DB, Glennon RA (January 1999). "Comparisons of hallucinogenic phenylisopropylamine binding affinities at cloned human 5-HT2A, -HT(2B) and 5-HT2C receptors". Naunyn-Schmiedeberg's Archives of Pharmacology. 359 (1): 1–6. doi:10.1007/pl00005315. PMID 9933142.
  10. 1 2 3 4 5 Rudin D, Luethi D, Hoener MC, Liechti ME (2022). "Structure-activity Relation of Halogenated 2,5-Dimethoxyamphetamines Compared to their α‑Desmethyl (2C) Analogues". The FASEB Journal. 36 (S1) fasebj.2022.36.S1.R2121. doi:10.1096/fasebj.2022.36.S1.R2121. ISSN 0892-6638.
  11. ↑ Glennon RA (1989). "Stimulus properties of hallucinogenic phenalkylamines and related designer drugs: formulation of structure-activity relationships". NIDA Research Monograph. 94: 43–67. PMID 2575229.
  12. ↑ 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.
  13. ↑ Glennon RA (1991). "Discriminative stimulus properties of hallucinogens and related designer drugs". NIDA Research Monograph. 116 (116): 25–44. PMID 1369672. Archived from the original on 2015-07-22. Retrieved 2015-06-29.
  14. ↑ Johnson MP, Hoffman AJ, Nichols DE, Mathis CA (December 1987). "Binding to the serotonin 5-HT2 receptor by the enantiomers of 125I-DOI". Neuropharmacology. 26 (12): 1803–1806. doi:10.1016/0028-3908(87)90138-9. PMID 3437942. S2CID 25077839.
  15. ↑ "Controlled Drugs and Substances Act". Department of Justice Canada. Retrieved 19 January 2026.