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PE 22-28 TREK-1 blocker, anyone following the preclinical antidepressant research

Posted by student748 in Research & News - 6 points, 4 comments.

Just came across the PE 22-28 page here (/peptides/pe-22-28) and spent a bit of time going down the rabbit hole. It is a spadin-derived peptide that blocks the TREK-1 potassium channel, and the preclinical angle is fast-acting antidepressant effects plus neurogenesis. Supposedly faster than SSRIs in animal models which, for what it is worth, sounds heaps promising but also exactly the kind of thing that gets overhyped before human data exists.

What caught my eye is the mechanism, TREK-1 blockade enhancing serotonergic signaling and synaptogenesis. That is a different pathway from what most mood-related peptides and nootropics target. I have no personal experience with this one, purely reading at this stage.

My concern is the safety profile is basically unknown in humans. No established dose, short half-life as a peptide, and the jump from animal depression models to actual human use is a big one. We have all seen compounds that looked brilliant in mice and went nowhere in people.

Keen to hear if anyone here has been following the research more closely or knows if there are any human trials queued up. Or is this still purely a lab tool at this point? Chur for any info.

Comments

  • labrat_vik: I haven’t tried PE‑22‑28 myself, just read the same preclinical stuff you did, and as a pharmacist the lack of any human data jumps out at me. gov and the EU registry a while back and didn’t see any registered studies, so it looks like it’s still a lab tool for now. The TREK‑1 angle is interesting because it’s a different route from the usual serotonergic or BDNF‑focused peptides, but the peptide’s short half‑life and unknown safety profile make me think twice before even considering a personal
  • student748: Chur for actually checking the trial registries, that is more than i did. Kinda what i expected though, the gap between animal models and human data on these things is massive. For what it is worth the short half-life is what gets me, like even if the mechanism is legit you'd be looking at frequent dosing which just adds more unknowns on top of unknowns. Did you come across anything about whether they are working on an analogue with longer half-life? Seemed like that was mentioned somewhere in
  • fasted_scientist: Ngl I haven’t touched PE‑22‑28 either, the preclinical data looks neat but the missing human safety and PK data make me wary. Have you seen any recent conference poster or abstract hinting at a phase I start? Would love to know if anything’s moved beyond the bench.
  • student748: Nah haven't found anything past the original rodent papers, been searching pretty hard too. Checked a couple of trial registries and nothing showing up which is not a great sign for how close this actually is to human studies. The PK gap you mentioned is the thing that really puts me off, short half-life peptides are tricky enough when you do have human data let alone without any. For what it is worth i reckon this one stays bench-only for a while yet. Keen to hear if anyone else has spotted so

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