MAOI chemistry question

[EmptyHand]

Can some informed chemist explain to me (or direct me to an explanation) as to why MAO breaks down DMT in the liver but not psilocybin even though they are chemically similar?

thanks!

eH

 

[joedirt]

Can some informed chemist explain to me (or direct me to an explanation) as to why MAO breaks down DMT in the liver but not psilocybin even though they are chemically similar?

thanks!

eH

It has to do with the conformation of psilocin. The free amine can bite back and stabilize on the 4 hydroxy.
What this means is that the conformation that can be oxidized by MAO is in far less abundance than say DMT which just has a free amine dangling into solution and no stabilizing 4 hydoxyl group. So it is oxidized by MAO...just slower.

I also suspect the conformational folding of psilocin helps it to cross the BBB...as polar compounds typically have a hard time crossing non polar membranes unless then can fold up and shield some of their charge.

Peace

 

[benzyme]

(of course) transporter proteins ferry psilocin, an amphipathic molecule, across the BBB.
indeed, it must be something about the binding active site of MAO-A (probably orientation of some lysine groups) that exclude 4-HO-DMT, but bind 5-HO-DMT.