Something that I have wondered for some time, why don’t we just give people in pain (esp. great pain) endorphins directly? Acquring some should be no problem. I know they can produce any living substance by just injecting it into the nucleus of a fast-replicating bacteria. And I assume nothing relieves pain better than naturally-occuring endorphins. So where am I wrong?
Thank you in advance to all who reply:)
Certainly not a silly idea, but some reasons why it may not be a workable solution to treat pain do present themselves:
The endorphins are peptides, which have great strengths and great drawbacks as drugs. Their biological activity can be superb, maybe unmatched. Afterall, these are often the natural ligands and signalling molecules that control our biological processes. Their pharmacology can be awful, though. They’re seldom orally bioavailable, as they would be rapidly degraded in the peptide-chopping up environment of the stomach. They have related issues with distribution and half-life. So you’d probably need an injection just to deliver an endorphin - OK in a hospital but not great anywhere else, and that’s without getting to other pharamcology issues it may have.
The endorphins are also signalling molecules which have a variety of roles and functions in the body. I think it would be an unusual strategy to use an endogenous signalling molecule like this as a therapeutic - it seems the risk of side effects would be massive, it doesn’t just do one thing [maybe someone can give a good counter-example here]. A better approach is to try and design a synthetic molecule that can agonise the particular receptor you want, and not have cross reactivity with receptors that you want to leave alone.
It is exceptionally hard to do this in the pain field, as an aside - one of the toughest if not the toughest areas of medicinal chemistry / pharmacology. Just look at the lack of genuine analgesics discovered in recent times.
This is sort of right if you’re talking about over-expressing particular proteins using a bacterium as a host organism - genetic engineering basically. The endorphins aren’t proteins though - they’re short peptides that aren’t made in the ribosome, so they’re distinct from the usual molecular biology approaches you’re alluding to. They could still be readily accessed, though. The enkephalins are short peptides that could be easily synthesised chemically. Something like beta-endorphin is a more challenging thing to get hold of - 31 amino acids, but any peptide sequence can be synthesised nowadays. You might have a problem f you wanted a lot of it, unless there is an easy way of isolating it from a natural source (not looked it up).
Interestingly, recent research has shown that morphine itself, the drug we isolated from the poppy, is actually made in our own bodies. This is something of a head scratcher and the consequences of the discovery are still being worked out. It’s an endogenous ligand of the opioid receptor, which sort of brings things full circle. Endorphin means endogenous morphine, but now it looks like morphine itself is endogenous. Confusing 
As Busy Scissors said, we have drugs that hit the endorphin receptors directly - they’re called opiates, e.g. morphine. I suppose the most major reason we don’t shift over to peptide-based opioid agonists is cost, benefit and potential risks. Opiates are dirt-cheap and we have centuries of experience with them. We now have other small-molecule drugs that are relatively specific to most of the different opioid receptors, so we can have selective effects if we desire, and don’t have a pressing need for peptide-based drugs to do that.
Bottom line, yes we can make them, yes we do make them (for research purposes), but none of them are currently as good as what you can make by purifying some opium poppy juice and throwing a few chemicals at it. Eventually, the hope is to create synthetic opioids that will let us have excellent pain control, no respiratory or digestive tract suppression, and no addictive potential. That’s a lot harder than just synthesizing a peptide that’s identical to one of the endogenous opioids, though.
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