Comment · Thu, November 22, 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 Once it's been o-demethylated to HHMA, it is no longer active like MDMA is.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
ricinuscommunis · 4 points
Do you think that 6-APB will be as or less neurotoxic than MDA? Or is that a question nobody could answer without a couple of decades of academic effort?
u/MisterYouAreSoDumb
I wrote to this in another post the other day. Given the limited studies and information on 6-APB, I would say that it's less neurotoxic than MDMA to 5-HT neurons. This is because it cannot be N-demethylated to MDA, so it's metabolites are not as dangerous. However, given the anecdotes I have read online, it seems that it causes more excitotoxicity than MDMA. A lot of people are getting uncontrolled muscle spasms after use.
EDIT: Oops, you asked compared to MDA. I would say it's definitely less neurotoxic than MDA for sure.