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Endorphins Releasers, do they exist?

Phobos

Phobos

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Oct 5, 2010
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As per title, we have many uOR agonists, but I never came across the existence of a drug that would act as a endorphins releaser or reuptake inhibitor.
Are drugs of this class impossible to make for any reason? Or maybe it would not make any sense to make them as they would be ineffective?
 
I'm not sure about an endorphin releaser type thing but I was reading about the concept of an endogenous opioid peptide reuptake inhibitor recently.

Apparently until recently it was thought that endorphins, enkephalins etc were degraded by an enzyme rather than being removed by a reuptake transporter.

But now there is research to suggest (it may be more than suggestive evidence but I can't remember so I'll just go with suggest) that there are reuptake transporters for opioid peptides.

Because of this there is ongoing research into developing drugs that inhibit the reuptake of endogenous opioid peptides as a novel way of treating pain and potentially other illnesses. But it'll be a long time before something like this comes into commercial use
 
You would think we would have discovered them before though. DRIs and SRIs we've known for a long time, so wouldn't we have run into some random molecules that do this? It makes me think it's not effective or practical.
 
Hey guys couldn't find the original article but I found this post which quotes some of the article. There's also a link to the the original article... which appears to be... broken :(

Selective Opioid Reuptake Inhibitors, that's an interesting idea | ScienceBlogs

Here is a interesting idea about how to treat pain without addicting people to pain killers. There is some back story to this business that you should know before we discuss why this is a cool idea, though.
scienceblogs.com scienceblogs.com

This is the part that's quoted on that site:

The idea that a transport system is involved is itself a novel concept. Conventional wisdom was that an enzyme was responsible for hydrolyzing, or decomposing, opiod peptide, Dr. Ganapathy says. This is the case for at least one neurotransmitter - acetylcholine, implicated in Alzheimer's - which is inactivated by an enzyme, rather than being transported back into the neuron like other neurotransmitters, such as serotonin, which has a role in depression.

But when he watched the activity of opiod peptides, he saw it actively taken back up into the neuronal cells.

Cloning the transporter and dissecting its molecular profile will ultimately provide a model for studying whether naturally occurring or designer drugs block this re-uptake. In fact, the National Institute on Drug Abuse will provide Dr. Ganapathy with a number of synthetic opiod peptides to see whether they are substrates, or blockers, of this transport system.
 
Apologies for having nothing to add but i find this idea very intersting and have wondered this myself(have searched for the same answer/question as op) so this post is really just a thread bump to keep it visible.
 
Exercise...

No but they exist. Nicotine. Probably most non-GABAergic euphoriants, as literature suggests. Enkphelinase inhibitors exist, some plant i can't recall the name of. B-endorphin is only one of the enodgenous opioids though. There's endomorphine and dynorphin, for example.

CBD is a mu/delta PAM. I don't know much of the bio behind opioids but I don't think reuptake happens with them the same as with monoamines.
 
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CBD is a mu/delta PAM. I don't know much of the bio behind opioids but I don't think reuptake happens with them the same as with monoamines.
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That's what we've been discussing above, apparently a reuptake system has been discovered for at least some endogenous opioid peptides
 
There are some articles from 1980s that claim there's a reuptake mechanism for met-enkephalin, but it's unclear how believable those claims were even at the time of publication.
 
Opioid peptides are not recycled like monoamine neurotransmitters. They are cleaved from propeptides that contain multiple other peptides. Monoamines are reuptaken for recycling purposes, they are packed into vesicles and re-released after uptake. It doesn't make sense for peptides to share such a mechanism.

That being said, I believe that there may be a transporter for endorphins and other peptides, but no data has shown if those are its main traffic, or simply passengers due to similarities to other peptides. Finally there is no data whatsoever on the fate of these peptides once inside the cell. They could be contributing to intracellular signalling or even being catabolized for their constituents.

If this re-uptake mechanism was valid, there would be a lot more research corroborating it, because its hella interesting and an extremely enticing drug target. The lack of people taking it further could be due to lack of techniques to study it, but it could also be because it is not a significant player in peptide signaling.

I think a lot of the compounds mentioned such as nicotine function by increasing the release of mu active peptides, not by inhibiting their reuptake.

I find it hard to believe that reuptake is a larger mechanism of terminating signalling than action of peptidases which are much more ubiquitous.
 
Garum does but likely more to a modulatory degree. It's a fermented fish brain and stomach extract that creates peptides for endorphin creation and/or release.
 
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I've never heard of garum as anything but a condiment, but it's the ancestor of Worcestershire sauce. In general fermented fish sauces are oh so good
 
You need ferment onions as well for the Worcestershire sauce.
I'm starting to think that the original recipe was a rubbish bin.
 
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