3,4,5-Trimethoxyamphetamine

3,4,5-Trimethoxyamphetamine

Clinical data
Other names	Trimethoxyamphetamine; TMA; TMA-1; 3,4,5-TMA; α-Methylmescaline; alpha-Methylmescaline; AMM; Mescalamphetamine; 3,4,5-Trimethoxy-α-methylphenethylamine
Drug class	Serotonergic psychedelic; Hallucinogen; Serotonin 5-HT2A receptor agonist
Identifiers
IUPAC name 1-(3,4,5-trimethoxyphenyl)propan-2-amine
CAS Number	1082-88-8
PubChem CID	31016
DrugBank	DB01516
ChemSpider	28775
UNII	P2K02L3YON
KEGG	C22747
ChEMBL	ChEMBL30336
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

Trimethoxyamphetamine (TMA or TMA-1), also known as 3,4,5-trimethoxyamphetamine (3,4,5-TMA), α-methylmescaline, or mescalamphetamine, is a psychedelic drug of the phenethylamine and amphetamine families.^[1][2] It is one of the trimethoxyamphetamine (TMA) series of positional isomers.^[1][2] The drug is notable in being the amphetamine (i.e., α-methylated) analogue of mescaline (3,4,5-trimethoxyphenethylamine).^[1][2]

TMA is said to be active at doses of 100 to 250 mg and to have a duration of 6 to 8 hours.^[1][3] 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.^[4] TMA's positional isomer 2,4,5-trimethoxyamphetamine (2,4,5-TMA or TMA-2) is much more potent than TMA, with a dosage of 20 to 40 mg and a duration of 8 to 12 hours.^[5]

TMA is a low-potency serotonin 5-HT_2A receptor partial agonist, with an affinity (K_i) of >12,000 nM, an EC₅₀Tooltip half-maximal effective concentration of 1,700 nM, and an E_maxTooltip maximal efficacy of 40%.^[6] Conversely, it was inactive at the serotonin 5-HT_1A, 5-HT_2B and 5-HT_2C receptors and at several other receptors, at least at the assessed concentrations (up to 10,000 nM).^[6] It showed affinity for the mouse and rat trace 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).^[6]

TMA is also a very low-potency serotonin releasing agent (SRA), with an EC₅₀ value of 16,000 nM.^[7] In contrast, it is inactive as a releasing agent and reuptake inhibitor of dopamine and norepinephrine (EC₅₀ > 100,000 nM).^[7] Despite its apparent SRA activity in vitro, TMA did not increase brain serotonin or dopamine levels in rodents in vivo.^[8] TMA is similarly inactive as a monoamine oxidase inhibitor (MAOI), including of both monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B) (IC₅₀Tooltip half-maximal inhibitory concentration > 200,000 nM).^[9][8]

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, an EC₅₀ of 10,000 nM, and an E_max of 56% in the same study.^[6] For comparison, DOM has shown an affinity (K_i) of 88 nM and an EC₅₀ of 4 to 24 nM.^[10]

• α-Ethylmescaline
• 3,4-Dimethoxyamphetamine