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 Once it's been o-demethylated to HHMA, it is no longer active like MDMA is.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
That's basically what I'm getting at. Feeling depleted and wonky, but no neurotoxic week+ come down effect. Breaking the oxygen carbon bond would release the double bond from the ring system. Ethylene moieties are really reactive. Of course we have little idea how (if at all) 6-APB is. It could also be that the benzofuran ring is too stable for enzymatic metabolism and any effects are indeed from excitotoxicity.
u/MisterYouAreSoDumb
Ohh ok, so you are postulating that CYP2D6 enzyme could break the oxygen carbon bond. I am not knowledgeable enough in that respect to know. It would be interesting to see some studies conducted on 6-APB. However, once that starts happening, it will probably get scheduled.