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2,5-Dimethoxyamphetamine - Wikipedia

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2,5-Dimethoxyamphetamine
Clinical data
Other names2,5-DMA; 2,5-Dimethoxy-α-methylphenethylamine; DMA; DMA-4; DOH; NSC-367445
Drug classSerotonin 5-HT2A receptor agonist
Identifiers

  • 1-(2,5-dimethoxyphenyl)propan-2-amine

CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.018.673 Edit this at Wikidata
Chemical and physical data
FormulaC11H17NO2
Molar mass195.262 g·mol−1
3D model (JSmol)

  • CC(CC1=C(C=CC(=C1)OC)OC)N

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

  • Key:LATVFYDIBMDBSY-UHFFFAOYSA-N

2,5-Dimethoxyamphetamine (2,5-DMA), also known as DMA-4 or as DOH, is a drug of the phenethylamine and amphetamine families.[1][2] It is one of the dimethoxyamphetamine (DMA) series of positional isomers.[1][2] The drug is notable in being the parent compound of the DOx (4-substituted-2,5-dimethoxyamphetamine) series of drugs.[1][2]

2,5-DMA is said to be inactive as a psychedelic, at least at the doses that have been assessed.[1][2] However, it has been reported to produce some stimulant-like effects, as well as sympathomimetic effects and mydriasis.[1][2] The dose range is said to be 80 to 160 mg and its duration is 6 to 8 hours.[1][2]

2,5-DMA is a low-potency serotonin 5-HT2A receptor partial agonist, with an affinity (Ki) of 2,502 nM, an EC50Tooltip half-maximal effective concentration of 160 to 2,352 nM (depending on the signaling cascade), and an EmaxTooltip maximal efficacy of 66%.[3] It has also been assessed at several other receptors.[3] The drug did not appear to bind to the monoamine transporters, at least at the assessed concentrations (up to 7,000 nM).[3] It was inactive at the human trace amine-associated receptor 1 (TAAR1).[3] 2,5-DMA shows dramatically reduced potency as a serotonin 5-HT2A receptor agonist compared to the DOx drugs, such as 2,5-dimethoxy-4-methylamphetamine (DOM).[3]

Though 2,5-DMA appears to be inactive or of very low potency as a psychedelic in humans, it is a highly potent anti-inflammatory drug similarly to other DOx and 2C drugs.[4][5] This was in spite of it being of very low potency as a serotonin 5-HT2A receptor agonist in terms of calcium mobilization in the study (EC50 = 3,548 nM; Emax = 109.0%).[4] Based on the preceding findings, Charles D. Nichols has said that both fully anti-inflammatory non-psychedelic compounds like 2,5-DMA and fully psychedelic non-anti-inflammatory compounds like DOTFM are known.[5]

  1. ^ a b c d e f Shulgin AT, Shulgin A (1991). "#54 2,5-DMA; DMA; 2,5-DIMETHOXYAMPHETAMINE". PiHKAL: A Chemical Love Story (1st ed.). Berkeley, CA: Transform Press. ISBN 9780963009609. OCLC 25627628.
  2. ^ a b c d e f Shulgin A, Manning T, Daley PF (2011). "#36. 2,5-DMA". The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds. Vol. 1. Berkeley: Transform Press. ISBN 978-0-9630096-3-0.
  3. ^ a b c d e Luethi D, Rudin D, Hoener MC, Liechti ME (2022). "Monoamine Receptor and Transporter Interaction Profiles of 4-Alkyl-Substituted 2,5-Dimethoxyamphetamines". The FASEB Journal. 36 (S1). doi:10.1096/fasebj.2022.36.S1.R2691. ISSN 0892-6638.
  4. ^ a b Flanagan TW, Billac GB, Landry AN, Sebastian MN, Cormier SA, Nichols CD (April 2021). "Structure-Activity Relationship Analysis of Psychedelics in a Rat Model of Asthma Reveals the Anti-Inflammatory Pharmacophore" (PDF). ACS Pharmacol Transl Sci. 4 (2): 488–502. doi:10.1021/acsptsci.0c00063. PMC 8033619. PMID 33860179. The nature of the 4-position substituent of phenethylamine psychedelics has been previously linked to 5-HT2 receptor selectivity as well as agonist properties at 5-HT2 receptors.40 Analysis of the 4-position demonstrated that the identity of the moiety at this position was rather flexible. Fully efficacious substitutions at the 4-position included the halogens iodine and bromine (R)-DOI (Figure 3), 2C-B (Figure 7A), methoxy (TMA-2) (Figure 7G), short-chain hydrocarbons (R)-DOM (Figure 7H), (R)-DOET) (Figure 7I), and a branched hydrocarbon (DOiBu) (Figure 7J). [...] In a comparison of PenH-AUC values determined for each drug as a proxy measure of anti-inflammatory efficacy (Figure 8A) to either EC50 or EMax for calcium mobilization downstream of 5- HT2A receptor activation (Table 1), [...]
  5. ^ a b Hamilton Morris (14 November 2021). "PODCAST 33: An interview with Dr. Charles D. Nichols". The Hamilton Morris Podcast (Podcast). Patreon. Event occurs at 48:22–53:56. Retrieved 20 January 2025.