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2,5-Dimethoxyamphetamine

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2,5-Dimethoxyamphetamine
Clinical data
Other names2,5-DMA; 2,5-Dimethoxy-α-methylphenethylamine; DMA; DMA-4; DOH; NSC-367445
Routes of
administration		Oral[1][2]
Drug classSerotonin 5-HT2A receptor agonist
Pharmacokinetic data
Duration of action6–8 hours[1][2]
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]

Use and effects

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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 orally and its duration is 6 to 8 hours.[1][2]

Pharmacology

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2,5-DMA activities
Target Affinity (Ki, nM)
5-HT1A 2,583
5-HT1B 8,435 (rat)
5-HT1D ND
5-HT1E ND
5-HT1F ND
5-HT2A 211–5,200 (Ki)
160–3,548 (EC50Tooltip half-maximal effective concentration)
58–109% (EmaxTooltip maximal efficacy)
5-HT2B 1,039 (Ki)
>10,000 (EC50)
ND (Emax)
5-HT2C 104–>10,000 (Ki)
3,144 (EC50)
76% (Emax)
5-HT3–5-HT7 ND
α1A, α1B–α1D ND
α2A–α2C ND
β1, β2 ND
D1 ND
D2 >7,000
D3–D5 ND
H1–H4 ND
M1–M5 ND
TAAR1 >10,000 (EC50) (human)
I1 ND
σ1, σ2 ND
SERTTooltip Serotonin transporter >7,000 (Ki)
ND (IC50Tooltip half-maximal inhibitory concentration)
ND (EC50)
NETTooltip Norepinephrine transporter >7,000 (Ki)
ND (IC50)
ND (EC50)
DATTooltip Dopamine transporter >7,000 (Ki)
ND (IC50)
ND (EC50)
MAO-ATooltip Monoamine oxidase A >100,000 (IC50)
MAO-BTooltip Monoamine oxidase B >100,000 (IC50)
Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: [3][4][5][6][7][8][9][10][11][12]

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 3,548 nM (depending on the signaling cascade and study), and an EmaxTooltip maximal efficacy of 66 to 109%.[6][8][9] It has also been assessed at several other receptors.[6] The drug did not appear to bind to the monoamine transporters, at least at the assessed concentrations (up to 7,000 nM).[6] It was inactive at the human trace amine-associated receptor 1 (TAAR1).[6] 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).[6]

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.[9][13] 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%).[9] 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.[13]

See also

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References

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  1. ^ a b c d e f g h 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 g h 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. ^ "Kᵢ Database". PDSP. 15 March 2025. Retrieved 15 March 2025.
  4. ^ Liu T. "BindingDB BDBM50005251 (+/-)2-(2,5-Dimethoxy-phenyl)-1-methyl-ethylamine::1-(2,5-dimethoxyphenyl)propan-2-amine::2,5-dimethoxy-4-bromoamphetamine::2-(2,5-Dimethoxy-phenyl)-1-methyl-ethylamine::2-(2,5-Dimethoxy-phenyl)-1-methyl-ethylamine(2,5-DMA)::CHEMBL8642::DMA". BindingDB. Retrieved 15 March 2025.
  5. ^ Nelson DL, Lucaites VL, Wainscott DB, Glennon RA (January 1999). "Comparisons of hallucinogenic phenylisopropylamine binding affinities at cloned human 5-HT2A, -HT(2B) and 5-HT2C receptors". Naunyn Schmiedebergs Arch Pharmacol. 359 (1): 1–6. doi:10.1007/pl00005315. PMID 9933142.
  6. ^ a b c d e f 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.
  7. ^ Dowd CS, Herrick-Davis K, Egan C, DuPre A, Smith C, Teitler M, et al. (August 2000). "1-[4-(3-Phenylalkyl)phenyl]-2-aminopropanes as 5-HT(2A) partial agonists". J Med Chem. 43 (16): 3074–3084. doi:10.1021/jm9906062. PMID 10956215.
  8. ^ a b Pottie E, Cannaert A, Stove CP (October 2020). "In vitro structure-activity relationship determination of 30 psychedelic new psychoactive substances by means of β-arrestin 2 recruitment to the serotonin 2A receptor". Arch Toxicol. 94 (10): 3449–3460. doi:10.1007/s00204-020-02836-w. hdl:1854/LU-8687071. PMID 32627074.
  9. ^ a b c d 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), [...]
  10. ^ 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". Br J Pharmacol. 136 (4): 510–519. doi:10.1038/sj.bjp.0704747. PMC 1573376. PMID 12055129.
  11. ^ Runyon SP, Mosier PD, Roth BL, Glennon RA, Westkaemper RB (November 2008). "Potential modes of interaction of 9-aminomethyl-9,10-dihydroanthracene (AMDA) derivatives with the 5-HT2A receptor: a ligand structure-affinity relationship, receptor mutagenesis and receptor modeling investigation". J Med Chem. 51 (21): 6808–6828. doi:10.1021/jm800771x. PMC 3088499. PMID 18847250.
  12. ^ Reyes-Parada M, Iturriaga-Vasquez P, Cassels BK (2019). "Amphetamine Derivatives as Monoamine Oxidase Inhibitors". Frontiers in Pharmacology. 10: 1590. doi:10.3389/fphar.2019.01590. PMC 6989591. PMID 32038257.
  13. ^ 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.
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