2,5-Dimethoxyamphetamine

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-Dimethoxyamphetamine

Clinical data
Other names	2,5-DMA; 2,5-Dimethoxy-α-methylphenethylamine; DMA; DMA-4; DOH; NSC-367445
Routes of administration	Oral[1][2]
Drug class	Serotonin 5-HT2A receptor agonist
Pharmacokinetic data
Duration of action	6–8 hours[1][2]
Identifiers
IUPAC name 1-(2,5-dimethoxyphenyl)propan-2-amine
CAS Number	2801-68-5
PubChem CID	62787
DrugBank	DB01465
ChemSpider	56526
UNII	OIM1536TQQ
KEGG	C22738
ChEMBL	ChEMBL8642
CompTox Dashboard (EPA)	DTXSID2091540
ECHA InfoCard	100.018.673
Chemical and physical data
Formula	C11H17NO2
Molar mass	195.262 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC(CC1=C(C=CC(=C1)OC)OC)N
InChI 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

Use and effects

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

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) 3,390–>10,000 (EC50) 93% (Emax)
5-HT2C	104–>10,000 (Ki) 3,144 (EC50) 76% (Emax)
5-HT3	ND
5-HT4	ND
5-HT5A	ND
5-HT6	ND
5-HT7	ND
α1A–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][13][14]

2,5-DMA is a low-potency serotonin 5-HT_2A receptor partial agonist, with an affinity (K_i) 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 E_maxTooltip maximal efficacy of 66 to 109%.^{[6][7] [10][11]} It has also been assessed at several other receptors.^[6][7] The drug did not appear to bind to the monoamine transporters, at least at the assessed concentrations (up to 7,000 nM).^[6][7] It was inactive at the human trace amine-associated receptor 1 (TAAR1).^[6][7] 2,5-DMA shows dramatically reduced potency as a serotonin 5-HT_2A receptor agonist compared to the DOx drugs, such as 2,5-dimethoxy-4-methylamphetamine (DOM).^[6][7]

2,5-DMA substitutes for DOM in rodent drug discrimination tests, albeit with dramatically lower potency than other DOx drugs, suggesting that it may have psychedelic-like effects at very high doses.^[15] Conversely, 2,5-DMA shows no substitution for dextroamphetamine in such tests, suggesting that it lacks psychostimulant- or amphetamine-like effects, at least in rodents.^[15]

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.^[11][16] This was in spite of it being of very low potency as a serotonin 5-HT_2A receptor agonist in terms of calcium mobilization in the study (EC₅₀ = 3,548 nM; E_max = 109.0%).^[11] 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.^[16]

See also

• Substituted methoxyphenethylamine
• 2,5-Dimethoxyphenethylamine (2C-H)
• 2,4,5-Trimethoxyamphetamine (2,4,5-TMA, TMA-2, or DOMeO)
• Anti-inflammatory § Serotonergic psychedelics