 | |
 | |
| Clinical data | |
|---|---|
| Other names | DON; 2,5-Dimethoxy-4-nitroamphetamine; 4-Nitro-2,5-dimethoxyamphetamine |
| Routes of administration | Oral[1][2][3] |
| Drug class | Serotonin5-HT2 receptoragonist;Serotonin 5-HT2A receptor agonist;Serotonergic psychedelic;Hallucinogen;Stimulant |
| ATC code |
|
| Pharmacokinetic data | |
| Onset of action | ≥1 hour[1][3] |
| Duration of action | 8–15 hours[1][4][3] |
| Identifiers | |
| |
| CAS Number | |
| PubChemCID | |
| ChemSpider |
|
| UNII | |
| ChEMBL | |
| CompTox Dashboard(EPA) | |
| 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] |
| |
| |
| (verify) | |
2,5-Dimethoxy-4-nitroamphetamine (DON) is apsychedelic drug of thephenethylamine,amphetamine, andDOx families.[1][4][2][3] Unlike related drugs likeDOB, it produces both pronouncedhallucinogenic andamphetamine-likestimulant effects.[1][2][3] The drug is takenorally.[1][2][3]
It acts as aserotonin5-HT2 receptoragonist, including of the serotonin5-HT2A receptor.[5] The drug produces psychedelic-like effects in animals.[6]
DON was first described in thescientific 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 byAlexander Shulgin in his 1991 bookPiHKAL (Phenethylamines I Have Known and Loved).[1] DON was encountered as a noveldesigner drug inJapan by the late 2000s.[8]
In his bookPiHKAL (Phenethylamines I Have Known and Loved),Alexander Shulgin lists DON's dose as 3.0 to 4.5 mgorally and itsduration as 8 to 15 hours.[1][4][2][3] The 3 mg dose produced mostlystimulant-like effects while the 4.5 mg dose produced fullhallucinogenic effects.[1][2][3] Itsonset was a little over 1 hour.[1][3] The duration of thepsychedelic effects was about 8 hours and the duration of thestimulation 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, intensevisual hallucinations, someauditory distortion, strongamphetamine-like stimulation, a frequent desire forphysical activity,anxiety,stomach cramps, slighthypothermia, and little or no physicalmalaise.[1][2][3] It was said to have very similar qualitative effects to those ofDOB 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 morerecreational potential.[1][2]
DON acts as aserotonin5-HT2A and5-HT2C receptorpartial agonist, albeit with far lowerpotency andefficacy than other DOx drugs.[5] It is also a serotonin5-HT2B receptorpartial agonist.[9] Earlier studies have also reported itsaffinities atserotonin receptors, including the serotonin5-HT2 and5-HT1 receptors.[10][11] It is inactive as amonoamine oxidase inhibitor (MAOI).[4] The drug produces thehead-twitch response, a behavioral proxy ofpsychedelic-like effects, in rodents.[6] It shows similar potency and efficacy as DOM in thisassay.[6]
DON is in a class of compounds commonly known as α-methylphenethylamines, oramphetamines and the full chemical name is 1-(2,5-dimethoxy-4-nitrophenyl)propan-2-amine.[1][4] It has astereocenter.[4]
DON is a relativelyhydrophilic compound.[3]
Thechemical synthesis of DON has been described.[1][4]
Analogues of DON include2C-N,2C-CN, and otherDOx drugs likeDOM andDOB, among others.[1]
DON was first described in thescientific 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 byAlexander Shulgin in his 1991 bookPiHKAL (Phenethylamines I Have Known and Loved).[1] DON was encountered as a noveldesigner drug inJapan by 2008 or 2009.[8]
DON is acontrolled substance inCanada under phenethylamine blanket-ban language.[12]
DON is listed as a Class A drug in theDrugs controlled by the UK Misuse of Drugs Act after the table of contents ofPiHKAL andTiHKAL were added to the schedules.
DON is not an explicitlycontrolled substance in theUnited States.[4] However, because of its close similarity in structure and effects toDOM andDOB, possession and sale of DON may be subject to prosecution under theFederal Analog Act.[citation needed]
(±)-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.
Table II. Affinities of Selected Phenalkylamines for 5-HT1 and 5-HT2 Binding Sites
