Chemistry:SeDMA

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SeDMA 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-benzoselenadiazole ring.[1] ODMA and TDMA 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-HT2A, 5-HT2B, and 5-HT2C 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]

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

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 "Bioisosteric analogs of MDMA: Improving the pharmacological profile?". J Neurochem 168 (9): 2022–2042. June 2024. doi:10.1111/jnc.16149. PMID 38898705. 
  2. ↑ 2.0 2.1 2.2 "Neurotoxicity of MDMA: Main effects and mechanisms". Exp Neurol 347. January 2022. doi:10.1016/j.expneurol.2021.113894. PMID 34655576. 
  3. ↑ "Survey of Selective Monoaminergic Neurotoxins Targeting Dopaminergic, Noradrenergic, and Serotoninergic Neurons". Handbook of Neurotoxicity. Cham: Springer International Publishing. 2022. pp. 159–198. doi:10.1007/978-3-031-15080-7_53. ISBN 978-3-031-15079-1. 
  4. ↑ "MDMA, serotonergic neurotoxicity, and the diverse functional deficits of recreational 'Ecstasy' users". Neurosci Biobehav Rev 37 (8): 1466–1484. September 2013. doi:10.1016/j.neubiorev.2013.04.016. PMID 23660456. 
  5. ↑ "Of mice and men on MDMA: A translational comparison of the neuropsychobiological effects of 3,4-methylenedioxymethamphetamine ('Ecstasy')". Brain Res 1727. January 2020. doi:10.1016/j.brainres.2019.146556. PMID 31734398. 
  6. ↑ "Neurological and cognitive alterations induced by MDMA in humans". Exp Neurol 347. January 2022. doi:10.1016/j.expneurol.2021.113888. PMID 34624331. https://researchonline.ljmu.ac.uk/id/eprint/15629/3/Montgomery_Roberts_2021%20Review.pdf. 
  7. ↑ 7.0 7.1 "The role of metabolism in 3,4-(+)-methylenedioxyamphetamine and 3,4-(+)-methylenedioxymethamphetamine (ecstasy) toxicity". Ther Drug Monit 26 (2): 132–136. April 2004. doi:10.1097/00007691-200404000-00008. PMID 15228153. 
  8. ↑ 8.0 8.1 "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. March 2001. doi:10.1007/s002130000645. PMID 11351932. 
  9. ↑ Holland, J., ed (2001). "Does MDMA Cause Brain Damage?". 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. https://www.erowid.org/chemicals/mdma/mdma_neurotoxicity1.shtml. 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." 



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