Bupe "Less is More" ... not so fast

[EastCoast]

Okay this actually makes perfect sense u did a good job BUT

It really made more sense to me wen u explained it in the sense of being more energetically accepting , but why would a drug with a lower binding affinity like a partial agonist beat out full agonist and out comepete it for the receptor??
Can u just explain why a lower binding affinity is more attracting for the receptor(s)

And does that mean any partial agonist would beat out any full agonist? Or can a full agonist have a lower binding affinity then some partials??

 

[Slow_Mobius]

Okay this actually makes perfect sense u did a good job BUT

It really made more sense to me wen u explained it in the sense of being more energetically accepting , but why would a drug with a lower binding affinity like a partial agonist beat out full agonist and out comepete it for the receptor??
Can u just explain why a lower binding affinity is more attracting for the receptor(s)

And does that mean any partial agonist would beat out any full agonist? Or can a full agonist have a lower binding affinity then some partials??

Binding affinity doesn't always correlate with efficacy. So a full agonist could have a higher binding affinity than a partial agonist, an antagonist could have a higher affinity than a full agonist, etc. It's just in this specific case that bupe, a partial agonist, has a higher binding affinity than most full agonists like morphine or heroin. It can get a little confusing because lower Kd means higher binding affinity. Bupe has a higher binding affinity so it outcompetes many full agonist opioids.

EDIT: I mixed up lower and higher in my last message! sorry for the added confusion. hopefully it makes a little more sense now

 

[browniejfam]

In my personal experience less is DEFINITELY more. I was on subutex for about a year, around 0.5mg a day. Usually insufflated twice a day and every dose gave me a decent buzz. I believe that using subs how I was lets the norbupe cross the BBB. I don't know the science behind this, but this is my experience.

 

[trunkofmycar]

Taking less also makes treating an injury like a broken leg easier. As in, reducing your pain with full agonists administered in the ER.

Ime keeping doses 2 mg or lower doesn't fully seem to 'block' full agonists... You can break through the bupe with a less ridiculous amount of any kind of full agonist.

I don't know much of the science behind this. I wondered if there is any situation where a high dose of bupe (say above 3 mg or so) is necessary? Where high doses work better, as opposed to just working equally to (or not as well) as a smaller dose.

Maybe high doses are purposefully prescribed so that you're always so full of bupe that you don't feel any -lift- whatsoever when dosing? Maybe that's part of the point of bupe therapy. Lol...?

 

[Beerman]

^ I agree with that Trunkofmycar, that Drs. overload people with bupe to block opiates basically, and they think their cravings will be less if a shitload of your receptors are occupied by bupe... that can may make sense at some point...

Also my 2 cents:
I've been in bupe mantaintment for like 6 years, and I think it's "basicaly like all drugs" with some *exceptions*. I explain:

If you keep your toleance low of any drug, when you feel your system is runing out of that drug, every time you redose you will feel better/stronger reward/effect than if your tolerance is skyrocketed by previous doses. Simply as that, right?

You will enjoy cocaine more, if you keep your tolerance down. You will enjoy LSD more if you keep your tolerance down, etc. Or am I wrong?

BUT also I agree that buprenorphine is "special" because of its partial agonism of mu opioid receptors, also its very high affinity, that brings us to the famous ceiling effect, and also that high binding affinity makes it very powerful by mass (weight), even if it is not a full agonist, it will activate a lot mu receptors to some point (0.4 over 1 or something like that if I'm not wrong) bc of its high affinity to the receptors....-chemistry, huh? 8(-

Norbupre is a full agonist, but it seems to poorly cross the BBB bc of its high affinity to that goddamn (lifesaver sometimes) protein G as you guys said... BUT it still might make its way to a mu receptor in the brain and activate it despite that, as Loperamide does, that last one maybe in even very smaller amounts...BUT it still will be overpowered by buprenorphine, but we need to remember that at the same time buprenorphine concentration levels decreases bc of metabolism into norbupe, norbupe concentration increases, so it gives it more chance to occupy a mu receptor, because there is less buprenorphine to compete with during time, even if it crosses the BBB in very small amounts, norbupe has also a very high affinity, so not much of it would be needed even if it's pump out of the brain...right?

All in all it's still a mystery to me how bupe *really* works. I just know that if I keep my tolerance low, I will enjoy more my bupes and if I double my dose I definitely feel something more...but not always pleasant bc of the nausea and low blood pressure, basically.

Hope all that makes sense...

And remember, keeping your tolerance down is always better