Comment · Thu, November 22, 2012
MDMA Neurotoxicity Part 1 (Metabolites)
Original post in this thread
MisterYouAreSoDumb · 77 points
This is probably going to be the first in a series of discussions I start about MDMA. There's just too much information for one post. Therefore, I am going to start with one that is very interesting to me: MDMA's metabolites and their role in neurotoxicity. I pre-appologise for the length and terminology used.
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First off, let's discuss how MDMA is metabolized. The human cytochrome CYP450 is responsible for the metabolism of MDMA. The primary enzyme responsible is CYP2D6, using O-demethylation. This process adds two hydrogen atoms to the two open oxygen atoms in MDMA to create HHMA. Let's look at the structure for a minute.
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MDMA is 3,4-methylenedioxy-N-methylamphetamine
HHMA is 3,4-dihydroxy-N-methylamphetamine
So your CYP2D6 enzyme added two hydrogen atoms to the methylenedioxy structure to create a dihydroxy structure. Once it's been o-demethylated to HHMA, it is no longer active like MDMA is. HHMA can then be 0-methylated further to HMMA, or 4-hydroxy-3-methoxy-N-methylamphetamine. Here is an image to help you visualize this process.
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handsomguy101 · 1 points
hey mister you are so dumb, I have seen your other posts and i must say bravo for taking the time to scour the internet for these important facts, though if I may add, these nuggets of information don't really help with the big picture. what I mean is that instead of telling us the small details, why not explain that dopamine can be oxidized into DOPAC which is at the route cause Parkinsons and dopamine related neurotoxicity, and then tell us how to stop that neurotoxicity, with something like selegiline which prevents neurotoxicity and will improve your rolls a LOT. in addition, the evidence that glutamate and ion channels are the cause of exitotoxicity is important, but irrelevant to most drugs including MDMA. any form of increased oxidative stress will open ion channels leading to an apoptic cascade so antioxidants are your primary concern, but unless you have a vitamin deficiency, or are dumb enough to take any sort of tryptophan supplement near the time of your roll, glutamate toxicity is extremely important.
what I might recommend as a trip supplement stack would be
magnesium
amino acid l-arginine and or l-ornothine(or just a good food source)
b-vitamins
Astaxanthin
and for the come down, the same thing
never ever use a tryptophan supplement unless you want NEUROTOXICITY ( just Google Quinolinic acid )
u/MisterYouAreSoDumb
I mentioned that this was just part 1. I have spoken to glutamate and calcium excitotoxicity in comments before though. I think this is actually my first post. Usually I just comment. I tried to keep this post strictly to 5-HT neurotoxicity, and the role metabolites play. I could type all night long if I did not limit myself, haha.
This post is where I spoke a little about excitotoxicity and supplements.
I've also had discussions about it in /r/Nootropics in regards to piracetam and it's use with MDMA and Amphetamine.
I agree that magnesium has to be a part of your supplementation. I use fully chelated magnesium glycinate. I could go on all night about the bioavailability of the various magnesium amino acid combinations, and their respective efficacies. However, my post was a wall of text as it is. I would love to discuss all of it with you though!