Peripheral receptor satiation, "more for the brain"

[Raihiar]

Good Morning fellow bluelighters

As mentioned in another thread of mine, i've got a load of questions that might stem from misunderstandings on my side, and i wanted to make sure i got it right.

So, once again let's assume there is a compound, that is a potent agonist on opioid-receptors, but can't cross the BBB (i.e. Loperamide) and i have taken enough of it to saturate my peripheral receptors. After that, i take a centrally active opioid with lower binding affinity than first compund. would more of that second compound make it to my brain / the receptors therein and work their magic there? or is that actually the reason why loperamide can be used to enhance the effects of certain opioids?

I hope what i wrote makes sense and i didn't just ramble because i didn't know better.

Raihiar

 

[Nagelfar]

I think I get the gist of what you're saying; if loperamide has taken up all of the spaces of the receptor sites in your gut / intestines; then does that mean a BBB penetrating opioid won't get as 'caught' on the ionic bonds in your gut (that are currently occupied with an overabundance of lope) and move more readily to your brain.

AFAIK I don't think it works quite like that, perhaps they associate for nanoseconds or so, but does that accrue to overall greater efficacy for the penetrative opioid enough to be noticeable? I can't say definitely, any other insights from others more versed in these sort of pharmacokinetics?

 

[Raihiar]

Yeah, i think you understood the question as intended. (sorry, english is not my first language)
well i felt the effects of my opioid of choice (Tilidine) to be stronger... of course that could have been placebo, me wanting to feel it, or a number of other subjective misinterpretations on my side.

 

[aced126]

I get what you are saying however the number of peripheral receptors is negligible compared to the total number of opioid molecules in a dose (in the 10^15 + range at least)

 

[belligerent drunk]

It is an interesting idea, however I believe aced is right in saying that the number of "extra molecules" that make it to the brain from this effect is negligible.

 

[Raihiar]

thanks for the answers

okay, i'll spin the thought some more and adjust the constellation mentioned in my opening post.

if someone took one compound that does make it throug the BBB and selectively attaches to Opioid subreceptors that don't contribute to the desired effects but are still targets for conventional opioids (e.g. maybe Morphine, but i don't know its binding data), would that maybe lower the threshhold-dose for minimal effects, based on the binding data of the opioid in question?

 

[serotonin2A]

thanks for the answers

okay, i'll spin the thought some more and adjust the constellation mentioned in my opening post.

if someone took one compound that does make it throug the BBB and selectively attaches to Opioid subreceptors that don't contribute to the desired effects but are still targets for conventional opioids (e.g. maybe Morphine, but i don't know its binding data), would that maybe lower the threshhold-dose for minimal effects, based on the binding data of the opioid in question?

The phenomenon you are asking about is technically known as "ligand depletion." The number of receptors in the body is much < the number of drug molecules, so ligand depletion is almost always a negligable factor in animals. This is true for morphine and other drugs.

 

[Raihiar]

Alright, so i've almost always had it the other way round.. i would have placed any bet that the receptors outnumber the drug molecules by orders of magnitude.

Thanks a lot for educating me a bit, i'm a long term creeper of the old ADD subforum and tried - and am still trying - to understand and learn as much as i could. - while at the same time studying pharmacy (but only 3 sem. :/ ) and subsequently beginnig and finishing a 4 yr. apprenticeship and work in a lab for mostly inorganic chemistry.

in about 6 Months i'll pick up studying again with a fresh (and mostly clean) start, and it feels like a dream coming true
i hope i'm much better equipped to finishing that, than at the first try six years ago..

only recently 'gathered the guts' to post and ask questions in NPD that wouldn't make me seem / feel like a totally ignorant beginner or whatever.

 

[Dresden]

I don't know about all you highly educated drug scientists or hardened heroin junkies, but I find 2 to 4 mg of loperamide occasionally feels almost identical to a standard sized dose of hydrocodone or oxycodone and, even, perhaps somewhat surprisingly not entirely UNlike a regular dose of heroin. I mean, you know, it's all in your head.

 

[belligerent drunk]

I don't know about all you highly educated drug scientists or hardened heroin junkies, but I find 2 to 4 mg of loperamide occasionally feels almost identical to a standard sized dose of hydrocodone or oxycodone and, even, perhaps somewhat surprisingly not entirely UNlike a regular dose of heroin. I mean, you know, it's all in your head.

What, on its own? I often take 2 to 6 mg of loperamide if I have a day ahead of me when I want to minimize the already minimal withdrawal I experience when abstaining from codeine for a prolonged period, and I can't say I feel anything even remotely like a medium dose of codeine.

 

[Raihiar]

I don't know about all you highly educated drug scientists or hardened heroin junkies, but I find 2 to 4 mg of loperamide occasionally feels almost identical to a standard sized dose of hydrocodone or oxycodone and, even, perhaps somewhat surprisingly not entirely UNlike a regular dose of heroin. I mean, you know, it's all in your head.

Well i can honestly say that what you described has never happened to me, neither this pronounced, nor at all, without co-administration of a low dose of tilidine.
and my tolerance / habit at the time wasn't anywhere near daily hydro or oxy (both of which are a bitch to even get your hands on + too dangerous for me.. might like em too much)