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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
3D model (JSmol)	Interactive image
SMILES N1SN=C2C=CC(=CC=12)CC(C)N()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

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. It is the analogue of MDMA in which the 1,3-benzodioxole ring has been replaced with a 2,1,3-benzothiadiazole ring. ODMA and SeDMA are closely related analogues. ODMA, TDMA, and SeDMA are releasing agents of serotonin, norepinephrine, and dopamine similarly to MDMA. 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. ODMA, TDMA, and SeDMA were first described in the scientific literature in June 2024.

MDMA and 3,4-methylenedioxyamphetamine (MDA) are well-known serotonergic neurotoxins that damage serotonergic neurons in the brain. However, MDMA and MDA injected directly into the brain have been found to not produce serotonergic neurotoxicity in rodents. This suggests that peripherally formed metabolites of MDMA and MDA may be the actual mediators of the neurotoxicity rather than MDMA and MDA themselves. 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. 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. As a result, ODMA, TDMA, and SeDMA might not share the serotonergic neurotoxicity of MDMA and MDA. However, more research is needed to assess this possibility. Moreover, other studies have found that slow infusion of MDMA directly into the brain does produce signs of serotonergic neurotoxicity.

See also

• Substituted methylenedioxyphenethylamine § Related compounds

References

1. ^ Alberto-Silva AS, Hemmer S, Bock HA, da Silva LA, Scott KR, Kastner N, Bhatt M, Niello M, Jäntsch K, Kudlacek O, Bossi E, Stockner T, Meyer MR, McCorvy JD, Brandt SD, Kavanagh P, Sitte HH (June 2024). "Bioisosteric analogs of MDMA: Improving the pharmacological profile?". J Neurochem. 168 (9): 2022–2042. doi:10.1111/jnc.16149. PMC 11449655. PMID 38898705.
2. ^ Costa G, Gołembiowska K (January 2022). "Neurotoxicity of MDMA: Main effects and mechanisms". Exp Neurol. 347: 113894. doi:10.1016/j.expneurol.2021.113894. hdl:11584/325355. PMID 34655576.
3. Kostrzewa RM (2022). "Survey of Selective Monoaminergic Neurotoxins Targeting Dopaminergic, Noradrenergic, and Serotoninergic Neurons". Handbook of Neurotoxicity. Cham: Springer International Publishing. pp. 159–198. doi:10.1007/978-3-031-15080-7_53. ISBN 978-3-031-15079-1.
4. Parrott AC (September 2013). "MDMA, serotonergic neurotoxicity, and the diverse functional deficits of recreational 'Ecstasy' users". Neurosci Biobehav Rev. 37 (8): 1466–1484. doi:10.1016/j.neubiorev.2013.04.016. PMID 23660456.
5. Aguilar MA, García-Pardo MP, Parrott AC (January 2020). "Of mice and men on MDMA: A translational comparison of the neuropsychobiological effects of 3,4-methylenedioxymethamphetamine ('Ecstasy')". Brain Res. 1727: 146556. doi:10.1016/j.brainres.2019.146556. PMID 31734398.
6. Montgomery C, Roberts CA (January 2022). "Neurological and cognitive alterations induced by MDMA in humans" (PDF). Exp Neurol. 347: 113888. doi:10.1016/j.expneurol.2021.113888. PMID 34624331.
7. ^ Monks TJ, Jones DC, Bai F, Lau SS (April 2004). "The role of metabolism in 3,4-(+)-methylenedioxyamphetamine and 3,4-(+)-methylenedioxymethamphetamine (ecstasy) toxicity". Ther Drug Monit. 26 (2): 132–136. doi:10.1097/00007691-200404000-00008. PMID 15228153.
8. ^ Esteban B, O'Shea E, Camarero J, Sanchez V, Green AR, Colado MI (March 2001). "3,4-Methylenedioxymethamphetamine induces monoamine release, but not toxicity, when administered centrally at a concentration occurring following a peripherally injected neurotoxic dose". Psychopharmacology (Berl). 154 (3): 251–260. doi:10.1007/s002130000645. PMID 11351932.
9. Baggott, Matthew; Mendelson, John (2001). "Does MDMA Cause Brain Damage?". In Holland, J. (ed.). Ecstasy: The Complete Guide: A Comprehensive Look at the Risks and Benefits of MDMA. Inner Traditions/Bear. pp. 110–145, 396–404. ISBN 978-0-89281-857-0. Retrieved 24 November 2024. While a single injection of MDMA into the brain (intracerebroventricularly) had no effect on TPH activity, slow infusion of 1 mg/kg MDMA into the brain over 1 hr produced enough oxidative stress to acutely reduce TPH activity (Schmidt and Taylor 1988). The acute decrease in TPH activity is an early effect of MDMA and can be measured at post 15 min (Stone et al. 1989b). TPH inactivation can also be produced by non-neurotoxic MDMA doses (Schmidt and Taylor 1988; Stone et al. 1989a; Stone et al. 1989b). It therefore appears that MDMA rapidly induces oxidative stress but only produces neurotoxicity when endogenous free radical scavenging systems are overwhelmed.

External links

• MDMA Variants Show Promise for Safer Psychotherapy - Neuroscience News
• New MDMA variants could be promising alternatives for safe psychotherapeutic applications - News Medical
• Utopian Pharmacology: Mental Health in the Third Millennium: MDMA and Beyond - 2024 Update - David Pearce

• Benzothiadiazoles
• Entactogens and empathogens
• Experimental drugs
• Serotonin-norepinephrine-dopamine releasing agents
• Serotonin receptor agonists
• Stimulants
• Substituted amphetamines