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 Once it's been o-demethylated to HHMA, it is no longer active like MDMA is.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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What they were answering
metocin · 1 points
Good info here!
What I'd really like to see is some concrete info on how this "neurotoxicity" (vaguest term ever award!) translates into real-world effects. Does it cause people to become forgetful? Moody? Hopelessly depressed? Develop Parkinson's? And is it permanent?
It's one thing to study brain changes in the lab and another to make the leap that something causes actual functional impairments. (Not that neurotoxicity is safe or good by any means. I personally feel that MDMA is not so benign and intuitively believe your statements to be true).
u/MisterYouAreSoDumb
My term was not vague. I was speaking directly to 5-HT, or serotonin, system damage. And I don't know about you, but I want to protect my brain from ANY damage, not just ones that I can noticeably see the effects of. MDMA induced 5-HT neurotoxicity is widely known to exist.
http://www.ncbi.nlm.nih.gov/pubmed/11473208
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1617070/
http://www.ncbi.nlm.nih.gov/pubmed/1684057
http://www.ncbi.nlm.nih.gov/pubmed/9135093
Frankly, I do not care if MDMA induced neurotoxicity is temporary, or only manifests itself later in life. I also don't care if mild damage may not cause easily recognized functional impairments. I want to figure out the mechanisms so that I can prevent the damage in the first place!