Comment · Thu, September 25, 2014
Blocking thioethers to prevent MDMA neurotoxicity?
Original post in this thread
fretworknetwork · 12 points
This is my first post to DrugNerds, so hi everyone!
I've been digging through the literature on MDMA neurotoxicity since I recently heard that direct injection of MDMA and MDA into the brain does not lead to any neurotoxicity. It seems like the current scientific consensus is that certain metabolites of alpha-MeDA and N-Me-alpha-MeDA are the real culprits, namely those that arise from interactions with glutathione (GSH) and N-acetylcysteine (NAC). I'm not a biochemist, so most of this is new to me and I'm figuring this out as I go along.
Are there ways of directly blocking glutathione and N-acetylcysteine temporarily that would prevent these metabolites from forming? Would alpha-MeDA and N-Me-alpha-MeDA instead be broken down into something else, or pass through the urine intact? Would there be horrific side effects of blocking these thioethers, given they are antioxidants that presumably have some important role in normal life (NAC, for instance, is apparently used as a drug to prevent liver damage. Sounds important to me.) I am also confused, since there is other evidence that antioxidants prevent or at least lessen MDMA neurotoxicity, and yet GSH and NAC are antioxidants. A…
What they were answering
Herperderperton · 1 points
Hey Mister, do you think the N-methylated versions of the thioesters are less neurotoxic than the non methylated versions. There seems to be evidence to suggest that [all are neurotoxic](www.sciencedirect.com/science/article/pii/S0306452207003491) Why then is it important to inhibit MDA formation, if MDMA gets metabolised to similar thioester neurotoxins without demethylation?
u/MisterYouAreSoDumb
Yes, they certainly are. However, they are hepatotoxic. This is why you still need antioxidants to handle those free radicals.