PE 22-28 showing rapid antidepressant effects in animal models, what y'all think?

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

Saw something about PE 22-28 the other day and it kinda stopped my scroll. It's this synthetic peptide that comes from spadin and blocks TREK-1 potassium channels. The wild part is how fast it seems to work in animal models, way faster than SSRIs, supposedly because it ramps up neurogenesis and serotonergic signaling almost right away.

For what it is worth, anything that promises "rapid antidepressant effects" gets my eyebrows up. SSRIs are great for some people and a slow miserable slog for others, so I get why folks are paying attention. But it is still preclinical, no human safety data, no real dose range worked out. So please do not treat this like the next great thing to run out and try...

The biohacker in me is curious though. A short half-life peptide acting on ion channels instead of serotonin reuptake is a different angle than most things floating around. Curious if anyone with more neuro background has thoughts on TREK-1 as a target, or if this looks like another flash in the pan once you dig into the literature.

Comments

• fasted_scientist: Yeah this one caught my eye too ngl. Spadin blocking TREK-1 is a cool mechanism on paper because it's not the usual "flood serotonin" approach, it's tweaking neuronal excitability instead. The rodent data does look rapid, like days not weeks, which is the whole point. That said, I'd want to see actual human PK before getting excited. Short half-life peptides are a nightmare to dose consistently, and TREK-1 isn't just in the hippocampus, it's all over the place (heart, vasculature, pain pathways
• curious_optimizer: Yeah the TREK-1 everywhere thing is exactly what gives me pause too. Tweaking excitability sounds clean till you remember that channel is doing stuff in like a dozen other places. And you're right about the half life, dosing peptides with a short window is just a headache waiting to happen for what it is worth. Human PK would answer a lot.
• grinder265: The half-life issue is real and that's kinda my worry too. Short-acting peptides that hit a channel expressed systemically is a different risk profile than something that crosses the BBB more selectively. Even if the rodent data looks clean you still have the translation problem of how humans handle it. I wanna see some basic PK work before anyone talks about stacking this.
• curious_optimizer: Oh for real, the PK question is the whole ballgame right now. Spadin-derived stuff has been floating around in the literature for years and nobody has really nailed down how long it sticks around in primates let alone humans. Channel expression being all over the place systemically is exactly what makes me nervous too... TREK-1 isn't just in the hippocampus, it's in cardiac tissue, smooth muscle, all kinds of places you don't necessarily want to be poking at with a short half-life compound.

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