Comment · Sat, November 24, 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.
_________________________________________________
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.
________________________________________________
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 Once it's been o-demethylated to HHMA, it is no longer active like MDMA is.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.
This is…
What they were answering
slyman928 · 1 points
yea but it seemed like you were saying that it was still the metabolites of MDA that made it neurotoxic also.
and yea in the context it's hard not to interpret it as disorder. i guess i could see it at like the condition was met in the certain people's genes. seems like kind of a stretch for me atm though lol.
u/MisterYouAreSoDumb
It is, it's just there is really no way to completely stop the O-demthylation or ring-hydroxylation completely. MDA is significantly more neurotoxicthan MDMA because of this. Antioxidants can help a lot though.