2,5-Dimethoxy-4-nitroamphetamine

vanc 6 verified verified 477211749 DON DON2DACS.svg skin-invert-image 235px Oral Serotonin 5-HT2 receptor agonist; Serotonin 5-HT2A receptor agonist; Serotonergic psychedelic; Hallucinogen; Stimulant None ≥1 hour 8–15 hours correct CAS 67460-68-8 105432 correct chemspider 95083 correct FDA 3FIV60666J correct EBI 8301 DON; 2,5-Dimethoxy-4-nitroamphetamine; 4-Nitro-2,5-dimethoxyamphetamine 1-(2,5-dimethoxy-4-nitrophenyl)propan-2-amine 11 16 2 4 COc1cc(c(cc1CC(C)N)OC)N(=O)=O correct chemspider 1S/C11H16N2O4/c1-7(12)4-8-5-11(17-3)9(13(14)15)6-10(8)16-2/h5-7H,4,12H2,1-3H3 correct chemspider JQJRESSXOVAECC-UHFFFAOYSA-N 206 207 (hydrochloride)231-232 °C ((R)-isomer) 2,5-Dimethoxy-4-nitroamphetamine (DON) is a psychedelic drug of the phenethylamine, amphetamine, and DOx families. DON Entry Shulgin A, Manning T, Daley P The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds Berkeley 1 2011 Transform Press 978-0-9630096-3-0 Unlike related drugs like DOB, it produces both pronounced hallucinogenic and amphetamine-like stimulant effects. The drug is taken orally. It acts as a serotonin 5-HT2 receptor agonist, including of the serotonin 5-HT2A receptor. The drug produces psychedelic-like effects in animals. DON was first described in the scientific literature by Ronald Coutts and Jerry Malicky by 1973. Coutts RT, Malicky JL The Synthesis of Some Analogs of the Hallucinogen 1-(2,5-Dimethoxy-4-methylphenyl)-2-aminopropane (DOM) Canadian Journal of Chemistry 51 9 1402–1409 1 May 1973 10.1139/v73-210 0008-4042 https://cdnsciencepub.com/doi/10.1139/v73-210 27 November 2025 Its properties and effects in humans were described by Juan Sebastian Gomez-Jeria and colleagues in the mid-1980s. Subsequently, the drug was reviewed by Alexander Shulgin in his 1991 book PiHKAL (Phenethylamines I Have Known and Loved). DON was encountered as a novel designer drug in Japan by the late 2000s. Uchiyama N, Miyazawa N, Kawamura M, Kikura-Hanajiri R, Goda Y [Analysis of newly distributed designer drugs detected in the products purchased in fiscal year 2008] Yakugaku Zasshi 130 2 263–270 February 2010 20118651 10.1248/yakushi.130.263 Japanese Use and effects In his book PiHKAL (Phenethylamines I Have Known and Loved), Alexander Shulgin lists DON's dose as 3.0 to 4.5mg orally and its duration as 8 to 15hours. The 3mg dose produced mostly stimulant-like effects while the 4.5mg dose produced full hallucinogenic effects.Gómez-Jeria, JS; Cassels, BK; Clavijo, R; Vargas, V; Quintana, R; Saavedra-Aguilar, JC. (1986). Spectroscopic characterization of a new hallucinogen: 1-(2,5-dimethoxy-4-nitrophenyl)-2-aminopropane (DON). Microgram 19 (11), 153–161. https://isomerdesign.com/bitnest/external/Microgram/19.11 "Here we can say that a dose of 4.5 mg of DON nitrate produces the standard effects described in the literature (10,11). The only qualitative difference between DON and its 4-Br analog (008) is that DON has a very strong stimulating action reminiscent of amphetamine. This action seems to reduce the incidence of insightful, and therefore potentially unpleasant experiences, and thus seems likely to appear on the market as an illicit recreational drug." Gomez-Jeria JS, Cassels BK, Saavedra-Aguilar JC A quantum-chemical and experimental study of the hallucinogen (±)-1-(2,5-dimethoxy-4-nitrophenyl)-2-aminopropane (DON) European Journal of Medicinal Chemistry 22 5 433–437 1987 10.1016/0223-5234(87)90032-8 https://repositorio.uchile.cl/handle/2250/160667 (±)-DON nitrate was subjected to preliminary screening by eight normal volunteers familiar with the effects of psychotropic substances, following published procedure [17]. Once the active dose level had been established, the number of subjects was increased to a total of 16 (12 male, 4 female, aged 21—51 years), with a total of 30 trials. [...] The subjects were asked to describe their experiences at the end of each session. [...] DON may be a potent hallucinogen, if its relatively poor lipid solubility does not prevent it from reaching the CNS efficiently. Acute oral administration of a total dose of 2 mg of the racemic nitrate (6.6 μmol) results, after a period of a little more than 1 h, in an amphetamine-like stimulated state. When 3 mg (10 μmol) are taken, these symptoms are maintained but stomach cramps and anxiety appear, the volunteers declaring that the general feeling is suggestive of the beginning of a hallucinogenic experience. At a total dose of 4.5 mg (15 μmol), the malaise is minimal or absent, and a psychedelic (not psychotomimetic) state ensues, with intense visual hallucinations, enhanced perception of color, slight hyperthermia and often a desire for physical activity. Visual and sometimes auditive distortions persist for about 8 h and amphetamine-like stimulation is usually present at least into the 14th h, although some subjects also reported longer-lasting psychedelic experiences. Its onset was a little over 1hour. The duration of the psychedelic effects was about 8hours and the duration of the stimulation was at least 14hours, although in some people the psychedelic effects were longer-lasting. The drug's effects were reported to include enhanced color perception, intense visual hallucinations, some auditory distortion, strong amphetamine-like stimulation, a frequent desire for physical activity, anxiety, stomach cramps, slight hypothermia, and little or no physical malaise. It was said to have very similar qualitative effects to those of DOB except for its additional strong stimulant component. Due to its pronounced stimulant effects, it was hypothesized that DON might have a reduced likelihood of potentially unpleasant and insightful experiences and thus might have more recreational potential. Interactions Psychedelic drug#Interactions Trip killer#Serotonergic psychedelic antidotes Pharmacology Pharmacodynamics DON acts as a serotonin 5-HT2A and 5-HT2C receptor partial agonist, albeit with far lower potency and efficacy than other DOx drugs. Acuña-Castillo C, Villalobos C, Moya PR, Sáez P, Cassels BK, Huidobro-Toro JP Differences in potency and efficacy of a series of phenylisopropylamine/phenylethylamine pairs at 5-HT(2A) and 5-HT(2C) receptors British Journal of Pharmacology 136 4 510–519 June 2002 12055129 1573376 10.1038/sj.bjp.0704747 It is also a serotonin 5-HT2B receptor partial agonist. Hemanth P, Nistala P, Nguyen VT, Eltit JM, Glennon RA, Dukat M Binding and functional structure-activity similarities of 4-substituted 2,5-dimethoxyphenyl isopropylamine analogues at 5-HT2A and 5-HT2B serotonin receptors Frontiers in Pharmacology 14 2023 36762110 9902381 10.3389/fphar.2023.1101290 free 1101290 Earlier studies have also reported its affinities at serotonin receptors, including the serotonin 5-HT2 and 5-HT1 receptors. 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 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 It is inactive as a monoamine oxidase inhibitor (MAOI). The drug produces the head-twitch response, a behavioral proxy of psychedelic-like effects, in rodents. Halberstadt AL, Chatha M, Klein AK, Wallach J, Brandt SD Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species Neuropharmacology 167 May 2020 31917152 9191653 10.1016/j.neuropharm.2019.107933 107933 It shows similar potency and efficacy as DOM in this assay. Chemistry DON is in a class of compounds commonly known as α-methyl phenethylamines, or amphetamines and the full chemical name is 1-(2,5-dimethoxy-4-nitrophenyl)propan-2-amine. It has a stereocenter. Properties DON is a relatively hydrophilic compound. Synthesis The chemical synthesis of DON has been described. Analogues Analogues of DON include 2C-N, 2C-CN, and other DOx drugs like DOM and DOB, among others. History DON was first described in the scientific literature by Ronald Coutts and Jerry Malicky by 1973. Coutts RT, Malicky JL The Synthesis of Some Analogs of the Hallucinogen 1-(2,5-Dimethoxy-4-methylphenyl)-2-aminopropane (DOM) Canadian Journal of Chemistry 51 9 1402–1409 1 May 1973 10.1139/v73-210 0008-4042 https://cdnsciencepub.com/doi/10.1139/v73-210 27 November 2025 Its properties and effects in humans were described by Juan Sebastian Gomez-Jeria and colleagues in 1986 and 1987. Subsequently, the drug was reviewed by Alexander Shulgin in his 1991 book PiHKAL (Phenethylamines I Have Known and Loved). DON was encountered as a novel designer drug in Japan by 2008 or 2009. Society and culture Legal status Canada DON 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 Kingdom DON is listed as a Class A drug in the Drugs controlled by the UK Misuse of Drugs Act after the table of contents of PiHKAL and TiHKAL were added to the schedules. United States DON is not an explicitly controlled substance in the United States. However, because of its close similarity in structure and effects to DOM and DOB, possession and sale of DON may be subject to prosecution under the Federal Analog Act.February 2013 See also DOx (psychedelics) Stimulant § Serotonin 5-HT2A receptor agonists Motivation-enhancing drug § Serotonin 5-HT2A receptor agonists References External links DON - Isomer Design DON Experience Reports - Erowid DON - PiHKAL - Erowid DON - PiHKAL - Isomer Design DON - The Shulgin Index The Big & Dandy DON Thread - Bluelight DON: A Tricky Psychedelic That’s Hard to Handle - Tripsitter Category:5-HT2A agonists Category:5-HT2B agonists Category:5-HT2C agonists Category:Designer drugs Category:DOx (psychedelics) Category:Nitrobenzene derivatives Category:PiHKAL Category:Psychedelic phenethylamines Category:Stimulants