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

Posted by student748 in Research & News - 2 points, 2 comments.

Stumbled on this peptide called PE 22-28 the other day, derived from spadin apparently, blocks a potassium channel called TREK-1. The claim is faster antidepressant effects than SSRIs in animal models plus neurogenesis and synaptogenesis. For what it is worth that mechanism sounds heaps more interesting to me than yet another serotonin reuptake approach, because it is targeting the channel rather than just flooding synapses with serotonin.

Checked the page here /peptides/pe-22-28 and it is straight up preclinical, no human dosing established, no human safety data. So yeah nah i am not about to go near it myself yet. But the neuroplasticity angle is what got my attention, especially for stroke recovery research. That is a pretty specific claim and i wonder how much of that is just rodent data being extrapolated.

My question is has anyone here been tracking TREK-1 research at all? Is this genuinely a new mechanism or just a repackaged version of what ketamine and other rapid-acting stuff already does through different pathways? Seems like every few months there is a new "fast antidepressant" candidate and most of them fizzle out. Keen to hear if anyone thinks this one is different or if it is just hype at this stage.

Comments

  • curious_scientist: I've been following TREK-1 stuff off and on since the spadin papers came out years ago. The mechanism is genuinely different from ketamine imo. Ketamine hits NMDA receptors and triggers a glutamate surge that leads to mTOR signaling and synaptogenesis. TREK-1 blockade is more direct, it changes neuronal excitability and BDNF expression through a totally different channel. So no, not just a repackaged version. But the stroke recovery angle is where I get skeptical. Most of that data is rodent mi
  • student748: Chur for that breakdown, the distinction between mTOR/glutamate surge vs direct excitability change makes sense, had not thought about it that way. And yeah the MCAO thing is exactly what i was worried about, rodent stroke models are notoriously rubbish for translation. For what it is worth that is kind of why i was keen to hear if anyone had seen anything beyond the animal stuff. Has there been any move toward human trials at all or is it still purely preclinical?

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