Comment · Sun, September 21, 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
Direct reply to the original post — see the thread post above.
u/MisterYouAreSoDumb
I'm on my phone on the way to lunch, or I'd comment further.
http://www.reddit.com/r/DrugNerds/comments/13lp0b/mdma_neurotoxicity_part_1_metabolites/
Read through that, and all my comments. The toxic metabolites have to conjugate with glutathione to have transport across the blood brain barrier. So yes it is an antioxidant. However, in a serendipitous twist, it actually creates 2,5-Bis-(glutathion-S-yl)-alpha-methyldopamine, which is what damages 5-HT axons. There's a lot more, though. I'll be able to talk more later.