2,5-Dimethoxy-4-fluoroamphetamine

Chemical compound vanc 6 verified verified 477211659 DOF DOF-2D-skeletal.svg skin-invert-image 200px DOF ball-and-stick structure.png bg-transparent 175px Oral Serotonin receptor modulator; Serotonin 5-HT2A receptor agonist; Stimulant; Possible psychedelic drug None Schedule I Class A correct CAS 125903-69-7 correct FDA 93WSW5GYR6 23844155 correct chemspider 23108678 correct EBI 267526 DOF; 2,5-Dimethoxy-4-fluoroamphetamine; 4-Fluoro-2,5-dimethoxyamphetamine 1-(4-fluoro-2,5-dimethoxyphenyl)propan-2-amine 11 16 1 1 2 CC(CC1=CC(=C(C=C1OC)F)OC)N correct chemspider 1S/C11H16FNO2/c1-7(13)4-8-5-11(15-3)9(12)6-10(8)14-2/h5-7H,4,13H2,1-3H3 correct chemspider NRANUECGGQVXOT-UHFFFAOYSA-N 2,5-Dimethoxy-4-fluoroamphetamine (DOF) is a serotonin receptor modulator and possible psychedelic drug of the phenethylamine, amphetamine, and DOx families. "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." Shulgin A, Manning T, Daley PF 2011 The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds Berkeley Transform Press 1 978-0-9630096-3-0 It is taken orally. The drug was encountered as a novel designer drug in Europe in 2015. https://isomerdesign.com/bitnest/external/EMCDDA/New-Drugs-In-Europe-2015 EMCDDA2016 isomerdesign.com 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. Glennon RA, Young R, Benington F, Morin RD 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 October 1982 7143352 10.1021/jm00352a013 In his more book Phenethylamine: von der Struktur zur Funktion and other publications, Daniel Trachsel lists the dose of DOF as 10mg or more orally. Trachsel D, Lehmann D, Enzensperger C 2013 Phenethylamine: von der Struktur zur Funktion de Nachtschatten-Science Solothurn Nachtschatten-Verlag 1 978-3-03788-700-4 https://books.google.com/books?id=-Us1kgEACAAJ 21 August 2025 https://archive.org/details/phenethylamine-von-der-struktur-zur-funktion-trachsel-lehmann-enzensperger-2013 Phenethylamines: From Structure to Function 858805226 He states that DOF produces stimulating effects at a dose of 6mg three times each spaced by 1hour (18mg total) orally based on initial anecdotal findings. Interactions Psychedelic drug#Interactions Trip killer#Serotonergic psychedelic antidotes Pharmacology Pharmacodynamics The receptor and transporter interactions of DOF have been characterized. Shannon M, Battaglia G, Glennon RA, Titeler M 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 June 1984 6479216 10.1016/0014-2999(84)90333-9 Glennon RA Central serotonin receptors as targets for drug research Journal of Medicinal Chemistry 30 1 1–12 January 1987 3543362 10.1021/jm00384a001 Table II. Affinities of Selected Phenalkylamines for 5-HT1 and 5-HT2 Binding Sites Nelson DL, Lucaites VL, Wainscott DB, Glennon RA 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 January 1999 9933142 10.1007/pl00005315 Rudin D, Luethi D, Hoener MC, Liechti ME Structure-activity Relation of Halogenated 2,5-Dimethoxyamphetamines Compared to their α‑Desmethyl (2C) Analogues The FASEB Journal 36 S1 2022 fasebj.2022.36.S1.R2121 0892-6638 10.1096/fasebj.2022.36.S1.R2121 free https://www.researchgate.net/publication/360423277 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. Glennon RA Stimulus properties of hallucinogenic phenalkylamines and related designer drugs: formulation of structure-activity relationships NIDA Research Monograph 94 43–67 1989 2575229 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. Trachsel D Fluorine in psychedelic phenethylamines Drug Testing and Analysis 4 7–8 577–590 July 2012 22374819 10.1002/dta.413 DOF more closely mimics the effects of the 4-unsubstituted 2,5-dimethoxyamphetamine than the effects of DOC, DOB, and DOI. Nichols DE, Frescas S, Marona-Lewicka D, Huang X, Roth BL, Gudelsky GA, Nash JF 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 7996545 10.1021/jm00051a011 Glennon RA Discriminative stimulus properties of hallucinogens and related designer drugs NIDA Research Monograph 116 116 25–44 1991 1369672 http://archives.drugabuse.gov/pdf/monographs/download116.html 2015-06-29 dead https://web.archive.org/web/20150722190934/http://archives.drugabuse.gov/pdf/monographs/download116.html 2015-07-22 Johnson MP, Hoffman AJ, Nichols DE, Mathis CA Binding to the serotonin 5-HT2 receptor by the enantiomers of 125I-DOI Neuropharmacology 26 12 1803–1806 December 1987 3437942 10.1016/0028-3908(87)90138-9 25077839 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 Legal status Canada DOF is a controlled substance in Canada under phenethylamine blanket-ban language.Controlled Drugs and Substances Act Department of Justice Canada https://laws-lois.justice.gc.ca/eng/acts/c-38.8/FullText.html 19 January 2026 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 DOx (psychedelics) References External links DOF - Isomer Design DOF - The Shulgin Index The Small & Handy DOF Thread - Bluelight DOF - First 7-trials a workup of an obscure potentially psychedelic amphetamine - Bluelight Category:5-HT2A agonists Category:5-HT2B agonists Category:Daniel Trachsel Category:Designer drugs Category:DOx (psychedelics) Category:Fluoroarenes Category:Psychedelic phenethylamines Category:Serotonin receptor agonists Category:Stimulants Category:Substituted amphetamines