2,4-Dimethoxyamphetamine

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| image = 2,4-DMA.svg

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| CAS_number = 23690-13-3

| CAS_supplemental =
52850-81-4

| PubChem = 141047

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| ChemSpiderID = 124411

| UNII = GT33R7Q58G

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| ChEMBL = 282734

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| synonyms = 2,4-DMA; 2,4-Dimethoxy-α-methylphenethylamine; DMA-3

| IUPAC_name = 1-(2,4-dimethoxyphenyl)propan-2-amine

| C=11 | H=17 | N=1 | O=2

| SMILES = CC(CC1=C(C=C(C=C1)OC)OC)N

| StdInChI = 1S/C11H17NO2/c1-8(12)6-9-4-5-10(13-2)7-11(9)14-3/h4-5,7-8H,6,12H2,1-3H3

| StdInChIKey = DQWOZMUBHQPFFF-UHFFFAOYSA-N

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2,4-Dimethoxyamphetamine (2,4-DMA), also known as DMA-3, is a drug of the phenethylamine and amphetamine families.{{Cite book | vauthors = Shulgin AT, Shulgin A | chapter = #53 2,4-DMA; 2,4-DIMETHOXYAMPHETAMINE | title = PiHKAL: A Chemical Love Story | date = 1991 | publisher = Transform Press | isbn = 9780963009609 | edition = 1st | location = Berkeley, CA | oclc = 25627628 | chapter-url = https://www.erowid.org/library/books_online/pihkal/pihkal053.shtml }}{{cite book | vauthors = Shulgin A, Manning T, Daley PF | chapter=#35. 2,4-DMA | title=The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds | publisher=Transform Press | location=Berkeley | volume=1 | year=2011 | isbn=978-0-9630096-3-0 | chapter-url=https://archive.org/details/shulgin-index-vol-1/page/54/mode/1up?view=theater }} It is one of the dimethoxyamphetamine (DMA) series of positional isomers.

It was reported by Alexander Shulgin to be active at a dose of 60{{nbsp}}mg orally and to produce threshold amphetamine-like stimulant and euphoric effects. However, there was also a "diffusion of association" and Shulgin stated that it was more than just a stimulant. The duration was described as short and effects subsiding at 3{{nbsp}}hours. Per Shulgin, the drug could be a full stimulant and/or a full psychedelic at sufficiently high doses, but higher doses were not pursued.

2,4-DMA has been found to act as a low-potency full agonist of the serotonin 5-HT_2A receptor, with an {{Abbrlink|EC₅₀|half-maximal effective concentration}} of 2,950{{nbsp}}nM and an {{Abbrlink|E_max|half-maximal effective concentration}} of 117%.{{cite journal | vauthors = Flanagan TW, Billac GB, Landry AN, Sebastian MN, Cormier SA, Nichols CD | title = Structure-Activity Relationship Analysis of Psychedelics in a Rat Model of Asthma Reveals the Anti-Inflammatory Pharmacophore | journal = ACS Pharmacol Transl Sci | volume = 4 | issue = 2 | pages = 488–502 | date = April 2021 | pmid = 33860179 | pmc = 8033619 | doi = 10.1021/acsptsci.0c00063 | url = }} It fully substitutes for DOM in rodent drug discrimination tests.{{cite journal | vauthors = Glennon RA, Young R | title = Comparison of behavioral properties of di- and tri-methoxyphenylisopropylamines | journal = Pharmacol Biochem Behav | volume = 17 | issue = 4 | pages = 603–607 | date = October 1982 | pmid = 6965276 | doi = 10.1016/0091-3057(82)90330-6 | url = }}{{cite journal | vauthors = Marcher-Rørsted E, Halberstadt AL, Klein AK, Chatha M, Jademyr S, Jensen AA, Kristensen JL | title = Investigation of the 2,5-Dimethoxy Motif in Phenethylamine Serotonin 2A Receptor Agonists | journal = ACS Chem Neurosci | volume = 11 | issue = 9 | pages = 1238–1244 | date = May 2020 | pmid = 32212672 | doi = 10.1021/acschemneuro.0c00129 | url = | quote = Removal of the 2- or 5-position methoxy group in 2,4,5-substituted compounds is also detrimental for their in vivo activity. For example, 2,4-dimethoxyamphetamine (13, Figure 2) and 3,4-dimethoxyamphetamine (14, Figure 2) are less potent than 8 in humans and in rats trained to discriminate 9. 14,15}} The drug is less potent in this regard than 2,4,5-trimethoxyamphetamine (2,4,5-TMA or TMA-2), but is more potent than 3,4,5-trimethoxyamphetamine (3,4,5-TMA or TMA-1).

2,4-DMA fails to produce stimulus generalization to dextroamphetamine in rodent drug discrimination tests, suggesting that it lacks psychostimulant- or amphetamine-like effects.{{cite journal | vauthors = Glennon RA | title = Stimulus properties of hallucinogenic phenalkylamines and related designer drugs: formulation of structure-activity relationships | journal = NIDA Res Monogr | volume = 94 | issue = | pages = 43–67 | date = 1989 | pmid = 2575229 | doi = | url = https://archives.nida.nih.gov/sites/default/files/monograph94.pdf#page=54}}