2,5-Dimethoxy-4-nitroamphetamine
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| Other names | DON; 2,5-Dimethoxy-4-nitroamphetamine; 4-Nitro-2,5-dimethoxyamphetamine |
| Routes of administration | Oral[1][2][3] |
| Drug class | Serotonin 5-HT2 receptor agonist; Serotonin 5-HT2A receptor agonist; Serotonergic psychedelic; Hallucinogen; Stimulant |
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| Pharmacokinetic data | |
| Onset of action | ≥1 hour[1][3] |
| Duration of action | 8–15 hours[1][4][3] |
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| Chemical and physical data | |
| Formula | C11H16N2O4 |
| Molar mass | 240.259 g·mol−1 |
| 3D model (JSmol) | |
| Melting point | 206 to 207 °C (403 to 405 °F) (hydrochloride) 231-232 °C ((R)-isomer)[1] |
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2,5-Dimethoxy-4-nitroamphetamine (DON) is a psychedelic drug of the phenethylamine, amphetamine, and DOx families.[1][4][2][3] Unlike related drugs like DOB, it produces both pronounced hallucinogenic and amphetamine-like stimulant effects.[1][2][3] The drug is taken orally.[1][2][3]
It acts as a serotonin 5-HT2 receptor agonist, including of the serotonin 5-HT2A receptor.[5] The drug produces psychedelic-like effects in animals.[6]
DON was first described in the scientific literature by Ronald Coutts and Jerry Malicky by 1973.[7] Its properties and effects in humans were described by Juan Sebastian Gomez-Jeria and colleagues in the mid-1980s.[1][2][3] Subsequently, the drug was reviewed by Alexander Shulgin in his 1991 book PiHKAL (Phenethylamines I Have Known and Loved).[1] DON was encountered as a novel designer drug in Japan by the late 2000s.[8]
Use and effects
[edit]In his book PiHKAL (Phenethylamines I Have Known and Loved), Alexander Shulgin lists DON's dose as 3.0 to 4.5 mg orally and its duration as 8 to 15 hours.[1][4][2][3] The 3 mg dose produced mostly stimulant-like effects while the 4.5 mg dose produced full hallucinogenic effects.[1][2][3] Its onset was a little over 1 hour.[1][3] The duration of the psychedelic effects was about 8 hours and the duration of the stimulation was at least 14 hours, although in some people the psychedelic effects were longer-lasting.[3]
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.[1][2][3] It was said to have very similar qualitative effects to those of DOB except for its additional strong stimulant component.[1][2][3] 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.[1][2]
Interactions
[edit]Pharmacology
[edit]Pharmacodynamics
[edit]DON acts as a serotonin 5-HT2A and 5-HT2C receptor partial agonist, albeit with far lower potency and efficacy than other DOx drugs.[5] It is also a serotonin 5-HT2B receptor partial agonist.[9] Earlier studies have also reported its affinities at serotonin receptors, including the serotonin 5-HT2 and 5-HT1 receptors.[10][11] It is inactive as a monoamine oxidase inhibitor (MAOI).[4] The drug produces the head-twitch response, a behavioral proxy of psychedelic-like effects, in rodents.[6] It shows similar potency and efficacy as DOM in this assay.[6]
Chemistry
[edit]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.[1][4] It has a stereocenter.[4]
Properties
[edit]DON is a relatively hydrophilic compound.[3]
Synthesis
[edit]The chemical synthesis of DON has been described.[1][4]
Analogues
[edit]Analogues of DON include 2C-N, 2C-CN, and other DOx drugs like DOM and DOB, among others.[1]
History
[edit]DON was first described in the scientific literature by Ronald Coutts and Jerry Malicky by 1973.[7] Its properties and effects in humans were described by Juan Sebastian Gomez-Jeria and colleagues in 1986 and 1987.[1][2][3] Subsequently, the drug was reviewed by Alexander Shulgin in his 1991 book PiHKAL (Phenethylamines I Have Known and Loved).[1] DON was encountered as a novel designer drug in Japan by 2008 or 2009.[8]
Society and culture
[edit]Legal status
[edit]United Kingdom
[edit]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
[edit]DON is not an explicitly controlled substance in the United States.[4] 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.[citation needed]
See also
[edit]- DOx (psychedelics)
- Stimulant § Serotonin 5-HT2A receptor agonists
- Motivation-enhancing drug § Serotonin 5-HT2A receptor agonists
References
[edit]- ^ a b c d e f g h i j k l m n o p q r s t Shulgin A, Shulgin A (September 1991). PiHKAL: A Chemical Love Story. Berkeley, California: Transform Press. ISBN 0-9630096-0-5. OCLC 25627628. DON Entry
- ^ a b c d e f g h i j k 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."
- ^ a b c d e f g h i j k l m n o Gomez-Jeria JS, Cassels BK, Saavedra-Aguilar JC (1987). "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. doi:10.1016/0223-5234(87)90032-8.
(±)-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.
- ^ a b c d e f g h 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.
- ^ a b Acuña-Castillo C, Villalobos C, Moya PR, Sáez P, Cassels BK, Huidobro-Toro JP (June 2002). "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. doi:10.1038/sj.bjp.0704747. PMC 1573376. PMID 12055129.
- ^ a b c Halberstadt AL, Chatha M, Klein AK, Wallach J, Brandt SD (May 2020). "Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species". Neuropharmacology. 167 107933. doi:10.1016/j.neuropharm.2019.107933. PMC 9191653. PMID 31917152.
- ^ a b Coutts RT, Malicky JL (1 May 1973). "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. doi:10.1139/v73-210. ISSN 0008-4042. Retrieved 27 November 2025.
- ^ a b Uchiyama N, Miyazawa N, Kawamura M, Kikura-Hanajiri R, Goda Y (February 2010). "[Analysis of newly distributed designer drugs detected in the products purchased in fiscal year 2008]". Yakugaku Zasshi (in Japanese). 130 (2): 263–270. doi:10.1248/yakushi.130.263. PMID 20118651.
- ^ Hemanth P, Nistala P, Nguyen VT, Eltit JM, Glennon RA, Dukat M (2023). "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 1101290. doi:10.3389/fphar.2023.1101290. PMC 9902381. PMID 36762110.
- ^ 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
- ^ 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.
External links
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