Does buprenorphine block endorphines?

[purplehaze147]

Would it block your brains natural endorphines since it blocks most opioids or is the binding affinity for them higher? I'm not sure if tolerance & dependence is due to a lack of endorphines or the down regulation of opioid receptors. Probably both right? In a non addicted person, in times when endorphines are released, would having bupe in the body make those activities less pleasureable?

 

[sekio]

versus DAMGO as a hot ligand it has about the same affinity for mu opioid receptors as beta endorphin does.
B-endorphin 1.6nM b-Endorphin vs DAMGO in cloned human mu receptors
buprenorphine 1.5nM vs DAMGO in cloned human mu receptors
ref:http://www.ncbi.nlm.nih.gov/pubmed/9686407 or the pdsp ki database.

given that most people don't take enough burpenorphine to fully saturate opioid receptors I would say no, it probably doesn't block all natural endorphin activity. doubly so at low (<2-4mg) doses where its metabolite norbuprenorphine probably plays a more major role. there is also the delta and kappa receptor and enkephalin/dynorphin as well (the respective peptide ligands). i don't think they are totally blocked either.

the other thing is that i don't think that endorphins are naturally delivered systematically upon release like opioid medication is, endorphins will have higher concentrations in the small area that they are released than the levels of buprenorphine you'd typically see in the brain from taking 2mg sublingually so any B-endorphin release will likely overwhelm buprenorphine's binding... i'm pretty sure endorphins are like any other neurotransmitter where they are more "local" signal chemicals than "natural drugs" and hence don't make it into central circulation as much as you'd imagine.

tolerance and dependence is caused by opioid receptor internalisation due to overactivation. i'm not sure if endorphin synthesis is heavily effected or not.