Opioids Bupe/norbupe and p-glycoproteins

[Speetz]

So I have always been intrigued by the relationship bupes effects have with its metabolite norbupe. Basically, if it's metabolized by 3A4 cyto, would an elevated amount of said cytochrome mean more metabolized norbupe, and therefore also more full agonist effect? Also, how much does it really affect the person, especially depending on dependency and tolerance, dose, etc.


So obviously this is a bit of neuroscience but being a sub dependent person and naturally curious about this sort of thing, I came across some info regarding p-glycoproteins and norbupe. Basically, they transfer out norbupe similar to the way they do loperamide, though probably to a much lesser extent.


So I know there are ways a very, VERY determined person can coat lope in nano-particled polysorbate 80 and crap to make it active by bypassing the protein transfers and stuff, so I am wondering if anyone knows of the extent norbupe is active or effected by glycoproteins? And would there be a way to lessen this, or would it even be worth it?


I assume not, but I am basically bringing this up for the intellectual discussion. I find it interesting, especially considering how complex the effect profile of bupe is even without considering norbupe anyway. I'll probably edit this with crap I forgot.


Any thoughts?

 

[Znegative]

I remember a post way back when where someone tried to do this with loperamide, they did something with crazy glue or something that had polysorbate 80, here is the thread I'm referring too. Obviously this seemed to be a very crude and dangerous practice.

I also find this kind of thing interesting, and it would be great (maybe) if we found a way to make our subs into a powerful full agonist. However (and forgive me for I don't have a great understanding of neuroscience or chemistry), wouldn't buprenorphine still have a higher binding affinity, and thus, block whatever norbupe could get through the BBB?

A lot of people say the reason why less buprenorphine is more in terms of opiate effect is possibly due to the fact that more norbupe can attach to empty receptors, but I for some reason don't really think that's the reason, I think it has more to do with the increased spike and drop in drug blood levels.

 

[Speetz]

Just a quick response. As far as the binding affinity, it's assumed norbupe has similar affinity. But I could be wrong; I'll have to look at a few things.