TMA

Clinical data
Other names	Trimethoxyamphetamine; TMA; TMA-1; 3,4,5-TMA; α-Methylmescaline; alpha-Methylmescaline; AMM; Mescalamphetamine; 3,4,5-Trimethoxy-α-methylphenethylamine; EA‐1319; EA1319; 3C-Mescaline; 3C-M
Routes of administration	Oral[1][2]
Drug class	Serotonergic psychedelic;Hallucinogen;Serotonin5-HT2A receptoragonist
ATC code	None
Legal status
Legal status	US: Schedule I[2][3]
Pharmacokinetic data
Duration of action	6–8 hours[1][2]
Identifiers
IUPAC name 1-(3,4,5-trimethoxyphenyl)propan-2-amine
CAS Number	1082-88-8
PubChemCID	31016
DrugBank	DB01516
ChemSpider	28775
UNII	P2K02L3YON
KEGG	C22747
ChEMBL	ChEMBL30336
CompTox Dashboard(EPA)	DTXSID00862529
Chemical and physical data
Formula	C12H19NO3
Molar mass	225.288 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC(CC1=CC(=C(C(=C1)OC)OC)OC)N
InChI InChI=1S/C12H19NO3/c1-8(13)5-9-6-10(14-2)12(16-4)11(7-9)15-3/h6-8H,5,13H2,1-4H3 Key:WGTASENVNYJZBK-UHFFFAOYSA-N

3,4,5-Trimethoxyamphetamine (TMA,TMA-1, or3,4,5-TMA), also known asα-methylmescaline (3C-mescaline or3C-M) ormescalamphetamine, is apsychedelic drug of thephenethylamine andamphetamine families.^[1][2] It is one of thetrimethoxyamphetamine (TMA) series ofpositional isomers.^[1][2] The drug is notable in being the amphetamine (i.e., α-methylated)analogue ofmescaline (3,4,5-trimethoxyphenethylamine).^[1][2]

TMA is aserotonergic psychedelic and produceshallucinogenic effects.^[1][2] It is said to be active at doses of 100 to 250 mg and to have aduration of 6 to 8 hours.^[1][4][5] For comparison,mescaline is typically used at doses of 200 to 500 mg and is said to have a duration of 10 to 12 hours or longer.^[6] TMA's positional isomer2,4,5-trimethoxyamphetamine (2,4,5-TMA or TMA-2) is much morepotent than TMA, with a dose of 20 to 40 mg and a duration of 8 to 12 hours.^[7]

TMA is a low-potencyserotonin5-HT_2A receptorpartial agonist, with anaffinity (K_i) of >12,000 nM, anEC₅₀Tooltip half-maximal effective concentration of 1,700 nM, and anE_maxTooltip maximal efficacy of 40%.^[11] Conversely, it was inactive at the serotonin5-HT_1A,5-HT_2B and5-HT_2C receptors and at several other receptors, at least at the assessed concentrations (up to 10,000 nM).^[11] It showed affinity for the mouse and rattrace amine-associated receptor 1 (TAAR1) (K_i = 1,800 nM and 3,200 nM, respectively), whereas it was inactive at the human TAAR1 (EC₅₀ > 10,000 nM).[11]

TMA is also a very low-potencyserotonin releasing agent (SRA), with anEC₅₀ value of 16,000 nM.[12] In contrast, it is inactive as areleasing agent andreuptake inhibitor ofdopamine andnorepinephrine (EC₅₀ > 100,000 nM).[12] Despite its apparent SRA activityin vitro, TMA did not increase brain serotonin or dopamine levels in rodentsin vivo.^[15] TMA is similarly inactive as amonoamine oxidase inhibitor (MAOI), including of bothmonoamine oxidase A (MAO-A) andmonoamine oxidase B (MAO-B) (IC₅₀Tooltip half-maximal inhibitory concentration > 200,000 nM).^[14][15]

The low potency of TMA as a serotonin 5-HT_2A receptor agonist is analogous to the case of mescaline, which is a well-known and widely used psychedelic but is likewise a very low-potency agonist of this receptor, showing an affinity (K_i) of 9,400 nM, anEC₅₀ of 10,000 nM, and anE_max of 56% in the same study.[11] For comparison,DOM has shown an affinity (K_i) of 88 nM and anEC₅₀ of 4 to 24 nM.[16]

TMA was firstsynthesized byGordon Alles around 1937.^[17][18] He assessed it in bothanimal studies andself-experiments and documented its effects, but these were not reported until 1959.^[17][18] The drug was first described in thescientific literature in 1947 and its psychedelic effects were first described in 1955.^{[19][20][21][22]} TMA was studied atEdgewood Arsenal under the code name EA‐1319 in 1953 and 1954.^[17] The drug was further characterized byAlexander Shulgin and described in his bookPiHKAL.^[1][2]

TMA is aSchedule Icontrolled substance in theUnited States.^[2][3]

• Substituted methoxyphenethylamine
• 3C (psychedelics) (4-substituted 3,5-dimethoxyamphetamines)
• α-Ethylmescaline (3,4,5-trimethoxy-α-ethylphenethylamine)
• Methyl-TMA (N-methyl-TMA)
• 3,4-Dimethoxyamphetamine (3,4-DMA)
• 4-PhPr-3,5-DMA

• TMA - Isomer Design
• TMA - PiHKAL - Erowid
• TMA - PiHKAL - Isomer Design

• Drugs not assigned an ATC code
• 3C (psychedelics)
• 5-HT2A agonists
• 5-HT2C agonists
• Alexander Shulgin
• Methoxy compounds
• Nicotinic acetylcholine receptor modulators
• PiHKAL
• Psychedelic phenethylamines
• Serotonin receptor agonists
• Serotonin releasing agents
• Sigma receptor modulators
• TAAR1 modulators

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• Articles with short description
• Short description is different from Wikidata
• Drugs with non-standard legal status
• Infobox drug articles with non-default infobox title
• Articles containing unverified chemical infoboxes