Comment · Mon, September 22, 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
fretworknetwork · 1 points
Although - hasn't other research shown that the metabolites of N-Me-[alpha]-MeDA are just as neurotoxic as the [alpha]-MeDA metabolites, for instance Capela et al (2007)? It's cool that you can block a significant amount of metabolism of MDMA to MDA just with grapefruit juice, but that's not the only problem pathway.
u/MisterYouAreSoDumb
The N-methylated metabolites cannot pass the blood brain barrier, though, with the exception of the ring-hydroxylated metabolite 2,4,5-THMA. They are for sure dangerous as well, and that is why you need antioxidants that can scavenge them. However, they are not as damaging as the non-N-methylated metabolites.