7-OH actually has a lower affinity for MOR than mitragynine itself, it is simply much more efficacious at activating the receptor, and has a lower chance of attaching as an antagonist.
Hey I was looking into that chart to see if the binding assay used a reference that would be comparable to buprenorphine, and those numbers absolutely did not come from the paper cited as #21.
The paper is available from sci hub (and it’s pretty impressive that both 7-OM (compound 12) mitragynine and the paeudoindoxyl (compound 2) were known then. Mitragynine was compound 1. The team doing that study did a few types of binding assays (and they didn’t label their values so I am assuming everything is nano-molar, as they compare to morphine (compound 4).
I cant find anything matching the numbers for mor/dor/kor receptors listed in the Wikipedia article even on a computer using ctrl + F (and playing around with the decimal point in case it was off due to the scientific notation).
The paper is on sci hub so you can see for yourself if you’d like, and i feel silly as I’m leaving this discussion with less information than when I posted. I’ll look and see if I can find the data anywhere though, as it’s a very interesting question.
Now for some hand wave-y explanations for why mitragynine derivatives could possibly be felt through suboxone even if they have a higher binding affinity. Take this with a grain of salt though.
Opioid receptors (such as the my) can signal through multiple downstream pathways, mainly either g-proteins or beta arrestin. Opioids which have a higher bias towards beta arrestin activation (compared to g-proteins) build up a tolerance more quickly and (controversially) induce more respiratory depression, for every unit of analgesia and euphoria. Fentanyl is typically considered a beta arrestin biased opioid, but it is still very active at the g-protein pathways.
Mitragynine and derivatives covered here have a very strong bias towards g-protein activation, barely inducing beta arrestin activity at the high end of their dose range.
This is of course something of a gross oversimplification (life is tricky), as there are multiple distinct types of beta arrestin and g-protein coupling that have different outcomes.
This paper compares opioids including fentanyl, buprenorphine , and morphine, and figure 3 has circular plots showing the level of activity at each signaling modality for each compound. Interestingly, fentanyl’s plot looks generally round, indicating high points for multiple beta arrestin modalities, but no lack of g-protein activation. Buprenorphine is extremely selective (the most selective of all the opioids they examined) for the g-protein pathways producing very little activation at the 6 beta arrestin pathway types.
Now this is the handwavey part, but that bias may be what lets the mitragynine relatives still produce an effect through buprenorphine’s presence. Agonism of a receptor is achieved by locking it into a conformation when you bind to it, and partial agonism is where the population of receptors can have flexibility between the inactive and active conformational states. The different downstream signaling modalities are each due to the conformation of the drug bound receptor. Ligand displacement is influenced by the receptor, so it is possible that the g-protein bias of the mitragynine derivatives may allow it to displace something like buprenorphine more easily than an equipotent (looking at old school receptor binding only) fentanyl derivative or something else with more beta arrestin character.
Edit: And one last thing!
This paper compares old school binding affinities of mitragynine, 7-OH mitragynine, buprenorphine, and friends (but not pseudoindoxyl) showing that they have much higher binding affinities than buprenorphine.
and open to any feed back or first hand experiences
