PE-22-28 is a 7-amino-acid research peptide engineered from spadin, a natural fragment of the sortilin receptor's propeptide. Its claim to attention is specific: it blocks the TREK-1 potassium channel about 300 times more potently than spadin itself (IC50 0.12 nM vs 40-60 nM), and in mouse models it produced antidepressant behavioral markers after 4 days of treatment — where SSRIs in the same paradigms take weeks.
Research-context information only. PE-22-28 is a research peptide. Protocols, doses, and reactions reported below come from published research and self-reported community sources. This article reports what has been documented, not what should be done. Consult a licensed physician for personal medical decisions.
Every efficacy finding below is preclinical — mouse behavior and in-vitro electrophysiology from one French research group (CNRS, Université Côte d'Azur). No human trial of PE-22-28 has been published. That makes it one of the most interesting and least human-validated compounds in the research-peptide catalog.
Why TREK-1 Is the Target
The rationale starts with genetics, not the peptide. Heurteaux et al., 2006 reported in Nature Neuroscience that mice lacking the TREK-1 background potassium channel showed a depression-resistant phenotype across five behavioral models, with increased serotonin neurotransmission and substantially reduced corticosterone elevation under stress.
A gene deletion that mimics antidepressant treatment suggested a drug that blocks the channel might do the same. The same group then identified spadin — a naturally occurring 17-residue fragment of the sortilin propeptide — as an endogenous TREK-1 blocker (Mazella et al., 2010, PLoS Biology).
Reported Benefits, Strongest Evidence First
Fast-onset antidepressant markers (mouse)
The defining spadin result: antidepressant-like behavioral effects after 4 days of treatment, versus the several weeks fluoxetine requires in the same mouse paradigms, alongside classical response markers — increased CREB activation and hippocampal neurogenesis (Mazella et al., 2010).
PE-22-28 reproduced this profile in the study that introduced it: reduced immobility in the forced-swim test, and after 4-day sub-chronic treatment, significantly reduced latency in the novelty-suppressed feeding test (Djillani et al., 2017, Frontiers in Pharmacology).
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