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A_D_E_P_Tyesterday at 11:42 AM1 replyview on HN

Isn't CYP2D6 inhibition the surer and more convenient route? Adding a bulky isopropyl group might reduce affinity at sigma1 receptors. Think about it: Going from 3-methoxy to 3-hydroxy makes for a very different drug. Wouldn't you expect that going from 3-methoxy to 3-isopropoxy would also make for a very different drug -- and not just "the same thing but more resistant to first-pass oral metabolism"?

Selective deuteration seems like another potential option with good prospects. Here it reduced CYP2D6 metabolism in a broadly similar case: https://pmc.ncbi.nlm.nih.gov/articles/PMC8724172/

Deuteration in a position like that is so simple that you can do it at home.


Replies

weare138today at 9:43 PM

I was curious and checked out the wikipedia page on CYP2D6 and it says CDB is also a strong CYP2D6 inhibitor but I don't have a formal background in this stuff.

https://en.wikipedia.org/wiki/CYP2D6#Ligands

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