Comment · Wed, November 28, 2012
MDMA Neurotoxicity Part 1 Metabolites)
Original post in this thread
MisterYouAreSoDumb · 129 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 Once it's been o-demethylated to HHMA, it is no longer active like MDMA is.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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What they were answering
ktheholehunter · 1 points
I guess consistent use is a little over played. It's more along the lines of sitting at String Cheese and taking a few dips from your neighbors bag.
u/MisterYouAreSoDumb
The problem is, that increases the risk of neurotoxocity greatly. Studies have shown that 200mg in one dose produces lower toxicity than 200mg spread over 4 doses. This is to do with the metabolism of MDMA by CYP2D6. Upon first dose, it binds to CYP2D6 and inhibits it. This causes more to be metabolized by CYP3A4 to MDA. If you are going to do it, make sure you keep drinking grapefruit juice. That will inhibit CYP3A4.