Overview
PE-22-28 is classified as a nootropic peptide peptide. Antidepressant, neuroplasticity, TREK-1 channel blockade, fast-acting mood elevation.
Synthetic hexapeptide fragment derived from the propeptide of sortilin, an endogenous regulator of the TREK-1 potassium channel. PE-22-28 competitively inhibits TREK-1, a background leak channel whose overactivation is implicated in depression and anxiety. By blocking TREK-1, PE-22-28 increases neuronal excitability in serotonergic circuits and promotes BDNF expression, producing rapid antidepressant effects in rodent models comparable to fluoxetine.
Also known as: Spadin analog, TREK-1 blocker
Category
Nootropic Peptide
Half-Life
1h
Route
SubQ
FDA Status
Not Approved
How Does PE-22-28 Work?
Synthetic hexapeptide fragment derived from the propeptide of sortilin, an endogenous regulator of the TREK-1 potassium channel. PE-22-28 competitively inhibits TREK-1, a background leak channel whose overactivation is implicated in depression and anxiety. By blocking TREK-1, PE-22-28 increases neuronal excitability in serotonergic circuits and promotes BDNF expression, producing rapid antidepressant effects in rodent models comparable to fluoxetine.
At the molecular level, PE-22-28 operates through pathways characteristic of the Nootropic Peptide class, interacting with target receptors and downstream signaling cascades to produce its observed effects.
Published Research
The following studies are indexed from PubMed and peer-reviewed journals:
[1]Spadin, a sortilin-derived peptide, targeting rodent TREK-1 channels: a new concept in the antidepressant drug design
Mazella et al. (PLOS Biology): Identifies spadin as a natural TREK-1 blocker with rapid antidepressant activity in rodent forced swim and tail suspension tests, matching SSRIs in efficacy with faster onset.
Evidence: preclinical[2]PE-22-28 antidepressant effects and neuroplasticity
Djillani et al.: PE-22-28, an optimized spadin analog, demonstrates superior TREK-1 inhibition, enhanced antidepressant effects in animal models, and upregulation of BDNF in hippocampus.
Evidence: preclinicalSafety Profile
⚠ PRECLINICAL RESEARCH ONLY. No human clinical trials completed. All efficacy data from rodent models. No validated human dosing, pharmacokinetics, or safety profile established.
| Side Effect | Incidence | Severity |
|---|---|---|
| Unknown in humans | Not established | rare |
Sourcing PE-22-28 for Research
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Full Research Profile
PE-22-28 — dosing, interactions, timelines & more
Comprehensive compound profile with sourcing information, stacking synergies, and outcome timelines.