Comment · Fri, November 23, 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 Once it's been o-demethylated to HHMA, it is no longer active like MDMA is.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
[deleted] · 2 points
Interesting, the reports I've seen are a more pronounced serotonin crash for a day or two but no long-term recovery. I worry about o-demethylation leading to a reactive c-c double bond which could be nasty.
u/MisterYouAreSoDumb
What do you mean O-demethylation? 6-APB has a benzofuran ring instead of a methylenedioxy ring. I'm not as familiar with organic chemistry as I would like. Can you explain how O-demethylation would lead to a double carbon bond?
Most of the anecdotes that I have seen, seem more indicative of excitotoxicity than 5-HT damage.