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 Once it's been o-demethylated to HHMA, it is no longer active like MDMA is.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
thenumber42 · 3 points
Good post! Do you by chance have any information about the half-life of the metabolites?
Here's a graph showing CYP2D6 polymorphisms, you can see that 5-10% is a poor CYP2D6 metabolizer!
http://www.primarypsychiatry.com/userdocs/ArticleImages/Preskorn_figure1%28big%29.jpg
u/MisterYouAreSoDumb
That's a very complex answer. It depends on the dosage you took, and the route of administration. There is going to be more first-pass metabolism if you take it orally. Intranasal and rectal will have less. It also depends on your polymorphisms. CYP2D6 and CYP3A4 both matter. I would say that the half life of the metabolites is between 10-15 hours after drop.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2774984/
Here is a study showing that body temperature drastically affected metabolism to MDA. So temperature plays a role here as well.