PE 22-28 and the TREK-1 blockade angle, anyone seen any new preclinical movement

Posted by student748 in Research & News - 9 points, 4 comments.

For what it is worth i keep coming back to the PE 22-28 stuff (/peptides/pe-22-28) because the mechanism is genuinely interesting to me. Blocking the TREK-1 potassium channel to boost serotonergic signaling and neurogenesis is a pretty different approach compared to just hitting 5-HT receptors directly like most psychedelics do. The animal data on rapid antidepressant effects being faster than SSRIs is the part that catches my attention but also the part i am most skeptical about because we have seen that story before with ketamine and look how complicated that turned out.

What i find promising is the neuroplasticity and synaptogenesis angle, could be relevant beyond just mood. But the human safety data is basically zero and it is still preclinical so anyone actually messing with this is way out ahead of the evidence. I have not tried it myself, keen to hear if anyone here has been following any newer papers or if it has stalled out in the pipeline.

Has anyone seen anything recent on this one or is it still sitting in that preclinical holding pattern? Just curious where it is at because the concept seems sound but the execution is a whole different story.

Comments

• labrat_vik: I haven’t messed with PE 22‑28 myself, mostly because the human safety sheet is basically blank and I prefer to let the animal work shake out first, I did notice a 2023 paper in Neuropharmacology where they gave mice a single dose and saw a quick rise in hippocampal BDNF and a forced‑swim improvement that lasted about 24 hours, which is faster than the usual SSRI timeline but still far from the rapid ketamine spike, the authors were careful to say it’s just a proof‑of‑concept and warned about of
• fasted_scientist: That cardiac rhythm flag is the bit that puts me off most tbh. TREK-1 isn't just in the brain, it's expressed in cardiac tissue too, and mucking about with potassium channels there is not something I'd want to gamble on based on mouse data alone. The BDNF finding is interesting but yeah, proof-of-concept in mice is a long way from anything I'd put in my body. Reckon anyone going early on this should at least have a proper ECG baseline, ngl.
• student748: Yeah nah that makes total sense. I didnt even think about the cardiac tissue expression, but that sounds like a massive red flag for what it is worth. The ecg baseline suggestion is a smart shout, though i reckon most people just wing it. Thanks for pointing out the potassium channel risk in the heart, definitely makes the bdnf gains feel way less worth the gamble. I will stick to reading the papers for now.
• student748: Cheers for the lead on that neuropharmacology paper, i will go have a read. The bit about cardiac rhythm is exactly why i am hesitant. For what it is worth i am more interested in the long term hippocampal bdnf stuff than a quick fix. If it is only lasting 24 hours in mice it might not even be worth the risk for humans. Do you reckon the potassium channel issues are a dealbreaker or just something to monitor with an ecg?

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