TDMA (drug)

This article is about TDMA the drug. For other uses, see TDMA (disambiguation).

TDMA is a bioisosteric analogue of 3,4-methylenedioxy-N-methylamphetamine (MDMA) which was developed in an attempt to create an improved MDMA alternative for potential clinical use.^[1] It is the analogue of MDMA in which the 1,3-benzodioxole ring has been replaced with a 2,1,3-benzothiadiazole ring.^[1] ODMA and SeDMA are closely related analogues.^[1] ODMA, TDMA, and SeDMA are releasing agents of serotonin, norepinephrine, and dopamine similarly to MDMA.^[1] However, they are less potent and efficacious in activating the serotonin 5-HT_2A, 5-HT_2B, and 5-HT_2C receptors than MDMA and show differing and potentially improved metabolic and pharmacokinetic properties in comparison.^[1] ODMA, TDMA, and SeDMA were first described in the scientific literature in June 2024.^[1]

TDMA

Clinical data
Other names	Thiadiazolylmethamphetamine; Thiadiazolyl-N-methylamphetamine
Drug class	Serotonin–norepinephrine–dopamine releasing agent; Entactogen; Stimulant
Identifiers
IUPAC name 1-(2,1,3-benzothiadiazol-5-yl)-N-methylpropan-2-amine
CAS Number	2302389-87-1
Chemical and physical data
Formula	C10H13N3S
Molar mass	207.30 g·mol−1
3D model (JSmol)	Interactive image
SMILES N1SN=C2C=CC(=CC=12)CC(C)N([H])C
InChI InChI=1S/C10H13N3S/c1-7(11-2)5-8-3-4-9-10(6-8)13-14-12-9/h3-4,6-7,11H,5H2,1-2H3 Key:VEEOETRMUTYYEO-UHFFFAOYSA-N

MDMA and 3,4-methylenedioxyamphetamine (MDA) are well-known serotonergic neurotoxins that damage serotonergic neurons in the brain.^{[2][3][4][5][6]} However, MDMA and MDA injected directly into the brain have been found to not produce serotonergic neurotoxicity in rodents.^[2][7][8] This suggests that peripherally formed metabolites of MDMA and MDA may be the actual mediators of the neurotoxicity rather than MDMA and MDA themselves.^[2][7][8] ODMA, TDMA, and SeDMA, with the exception of N-demethylation, do not share any of the phase I or phase II metabolic pathways of MDMA.^[1] Notably, in contrast to MDMA, methylenedioxy ring opening and consequent formation of catechol metabolites, which have been linked with free radical generation, does not occur.^[1] As a result, ODMA, TDMA, and SeDMA might not share the serotonergic neurotoxicity of MDMA and MDA.^[1] However, more research is needed to assess this possibility.^[1] Moreover, other studies have found that slow infusion of MDMA directly into the brain does produce signs of serotonergic neurotoxicity.^[9]

See also

• Substituted methylenedioxyphenethylamine § Related compounds