ResearchSafe

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

Posted by student748 in Research & News - 5 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 animal data on rapid antidepressant effects looks genuinely interesting. Faster than SSRIs in those models, which is a big claim but the mechanism at least makes sense to me, TREK-1 inhibition boosting serotonergic signaling and neurogenesis.

For what it is worth i am a bit torn. The neuroplasticity angle is appealing and i can see why people tracking longevity and brain health would be keen. But it is still preclinical, no established human dosing, and the safety profile is basically unknown. That is a pretty big gap before anyone should be messing with it.

The thing i keep wondering about is whether the synaptogenesis claim actually translates to anything a human would notice, or if it is one of those things that looks great in rodents and goes nowhere in people. Has anyone here been following the TREK-1 research more closely, or seen any human data i might have missed? Keen to hear what people think about the promise vs the hype here.

Comments

  • fasted_scientist: I keep coming back to this one and ngl the mechanism is sound but that's about where my enthusiasm stops. TREK-1 knockout mice show reduced depression-like behaviour, sure, but we've seen this story play out before with plenty of promising targets that crumbled in human trials. The spadin work from the French group (Borsotto et al) is basically the whole foundation here and it's all rodent or in vitro. The synaptogenesis question you're asking is the right one. Even if it happens in humans, whe
  • labrat_vik: I hear you on the mouse data, it always seems to fall apart once you move into actual human complexity, and the leap from rodent behavior to human mood is huge. I wonder if the synaptogenesis would even feel like anything different to a person, or if it just ends up being another slow way to feel slightly better.
  • student748: Yeah nah that is exactly what i was getting at, cheers for putting it better than i did. The "slightly better" thing is real, like maybe you just feel a touch more resilient over weeks and would never know if it was the peptide or just life being less shit that month. For what it is worth the rapid onset claim in the animal models is what makes it different from ssri timelines, but whether a human would even clock that difference, i genuinely have no idea. Has anyone here actually run it yet or
  • student748: Yeah nah that is exactly where i land too, the borsotto stuff being the entire foundation is a bit thin. The SSRI comparison is a i had not thought about, if we can barely tell whether synaptogenesis from those is doing anything subjectively then pe 22-28 would be even harder to read. For what it is worth do you reckon there is anything in the pipeline closer to human trials on this target, or is it pretty much just the french group still?

Community discussion - research and educational context only. Not medical advice.