Peptide psychedelics

[Lombergerh]

So i wonder, we have peptide opiates is there any studies or articles about peptide psychedelics substance?

 

[atara]

The critical difference is that the opioid receptors naturally respond to peptides (endorphins), whereas the serotonin (psychedelic) receptors have naturally small-molecule ligands. That doesn't mean it's impossible, just not terribly likely.

 

[Solipsis]

Ergotamine comes close...
And then there's dermorphin, that doesn't contradict atara because it works via opioid mechanism. I don't think it is really psychedelic though but I would expect another unknown *new* psychedelic peptide to be active either via opioid or cannabinoid receptors yea.

 

[sekio]

I cannot see any reason to deny the existience of psychedelic peptides; that said, I doubt there are any extant 5-ht2a agonist peptides in use today.

The ergopeptines are indeed peptide-derived, but they're still far enough from the effects of LSD/LSA.

 

[crazycatman]

I think we're just beginning to discover the things that can be done with peptides (seriously peptides are one of the new and exiting things in medicine). My guess is that eventually there will be a peptide with psychedelic properties. I could see some problems with it, mainly it being a bit unstable and it having to be injected, but that's just a guess.

 

[Hammilton]

The ergopeptines aren't exactly what we usually thing of as peptides. Yeah, there's a peptide bond in there, but mostly we think of amino acids. Sure, there were amino acids joined to that thing at one point during the biosynthesis of them, but the final ergopeptine bears little resemblance to the amino acids it was formed from.

Why does there "have" to be peptide psychedelics? This is a receptor that has evolved to be activated by serotonin, a small molecule, and seems to be most strongly activated by a very rigid derivative of that small molecule- a derivative that is still very small compared to even the small pentapeptide enkephalins.

It's true that morphine and fentanyl are both small molecules, binding to a receptor which naturally accepts pentapeptides like met-enkephalin, but that's looking at it backwards.

You may be able to pick a lock with a small screwdriver and a paperclip,* but you can't do the same thing with your fingers which won't fit into the keyhole. I seriously doubt there will ever be peptide psychedelics for that reason. MAYBE you could get a pentapeptide to bind, but that's really unlikely too. The receptor has such stringent requirements for what works. It's not nearly as promiscuous as GABA, which I'd be surprised if there's not a small peptide which could bind to it.


(screwdriver turns the lock, putting on some pressure, the paperclip depresses the pins and as it's withdrawn, allows the pins to rebound back into place. Done carefully and correctly, they'll only slide back out to the proper level because of the rotational pressure. If they all fall into place and are held well, it'll open)

 

[Deleted member 170540]

There seem to exist peptide dopamine reuptake inhibitors, even though the natural DA transporter ligand dopamine is a small non-peptide molecule, see http://www.sysbio.ac.cn/pdf/2006/7.pdf .

Also, some large peptides like bungarotoxins bind to acetylcholine receptors.