PE-22-28
Spadin-derived synthetic peptide (TREK-1 channel blocker)
A synthetic peptide analog of spadin referenced in mood and neuroplasticity research.
Also referenced as: PE22-28, Spadin analogue
Overview
PE-22-28 is a synthetic peptide derived from spadin, itself a fragment of the sortilin-derived propeptide (neurotensin receptor-3 propeptide), developed in academic pharmacology research primarily in France.
At a glance
What PE-22-28 does
PE-22-28 is a synthetic seven-residue peptide ("mini-spadin"), corresponding to residues 22-28 of spadin, itself a natural fragment cleaved from the sortilin propeptide. It was engineered by French researchers to keep spadin's useful activity while improving stability and potency. What it does in research is produce fast-onset antidepressant-like effects and promote hippocampal neurogenesis in animal models, positioning it as a mechanistically distinct alternative to conventional antidepressants.
Its mechanism is selective inhibition of the TREK-1 potassium channel. TREK-1 is a background (leak) potassium channel whose activity tends to reduce neuronal excitability and serotonergic signaling; by blocking it, PE-22-28 increases the excitability and serotonin output of circuits in the dorsal raphe and prefrontal cortex, which is broadly the system SSRIs modulate but reach only slowly and indirectly. Shortened spadin analogs like PE-22-28 have been reported to show stronger TREK-1 inhibition, better in-vivo stability, and greater antidepressant activity than spadin itself. Downstream, the increased serotonergic tone is associated with enhanced neurogenesis and synaptic markers.
The evidence is entirely preclinical. In rodent behavioral paradigms, antidepressant-like effects appear within roughly four days of dosing, far faster than the multi-week onset of SSRIs, and hippocampal neurogenesis is increased. However, there are no completed, published human efficacy trials, so its antidepressant and cognitive effects in people are unproven and its safety profile in humans is unknown.
Effects reported in research
- Selective inhibition of the TREK-1 background potassium channel (in-vitro/preclinical).
- Fast-onset antidepressant-like behavior in rodent models, within about four days of dosing (animal).
- Increased serotonergic signaling in dorsal raphe and prefrontal-cortex circuitry via TREK-1 blockade (preclinical).
- Enhanced hippocampal neurogenesis in animal studies (animal).
- Stronger TREK-1 inhibition and better in-vivo stability than the parent peptide spadin (preclinical).
- Associated increases in synaptic/plasticity markers accompanying antidepressant-like effects (animal).
- No completed, published human efficacy trials; all antidepressant and cognitive effects remain preclinical.
- Human safety and dosing profile not established.
Effects listed reflect findings reported in the research literature — many in animal or in-vitro models. Listing an effect is not a claim of efficacy or a therapeutic indication in humans.
Mechanism of action
PE-22-28 is a shortened, modified analog of spadin designed to block the TREK-1 (two-pore-domain potassium) channel. Blockade of TREK-1 is associated in preclinical research with antidepressant-like effects and enhanced neurogenesis and synaptogenesis. It was engineered to improve stability relative to the parent spadin peptide.
Mechanistic description reflects published research-literature understanding. Much peptide research is preclinical (in-vitro or animal-model); mechanism in humans may differ and is not established for many compounds.
What it's studied for
Research contexts in which PE-22-28 appears in the literature. Listing a research area is not a claim of efficacy or a therapeutic indication.
Key characteristics
- Derived from spadin, a naturally occurring TREK-1-modulating peptide fragment
- Acts as a TREK-1 (two-pore-domain K+) channel blocker
- Studied preclinically for rapid antidepressant-like effects
- Engineered for improved metabolic stability over spadin
- Research-only; no approved human clinical use
Reported research dosing reference only
Educational reference, not dosing guidance. The figures below summarize amounts reported in published research and research-community protocols, provided for educational and research context only. They are not medical advice, not a recommendation, and not instructions for human use. PE-22-28 is a research compound.
No validated human dose exists; reported figures are community-derived microgram ranges rather than trial-anchored values. These are reference figures for research context only, not human dosing guidance.
Preclinical only; no completed human trials, no validated human dose or established human half-life
How it compares
PE-22-28 is distinguished by its ion-channel (TREK-1) blocking mechanism aimed at antidepressant effects, unlike the neurotrophic or melanocortin peptides in this class.
Commonly studied alongside
Compounds frequently researched together with PE-22-28 in the literature. Cross-referenced for research context — not a usage or combination recommendation.
Compare and calculate
Side-by-side pages for the pairings the literature already documents for PE-22-28, plus the unit-conversion reference for a reconstituted vial. Factual comparisons of documented characteristics — not a recommendation to combine or use any compound.
PE-22-28 reconstitution calculator → Concentration, volume per measured amount and syringe units for a stated vial mass and diluent volume. A unit-conversion reference, not a dosing recommendation.
Handling & Stability
Lyophilized peptides are stored cold, protected from light, and reconstituted only at the time of intended in-vitro work.
- Avoid repeated freeze-thaw cycles
- Verify supplier lot and Certificate of Analysis
- Follow institutional lab-safety protocols
Analytical & COA Concepts
Reputable research suppliers publish a third-party Certificate of Analysis per batch. Key analytical concepts referenced in COAs include:
Category Context
PE-22-28 sits in the Cognitive & Nootropic area of the PeptiDex library.
- Entry type: Research compound reference
- Cognitive & Nootropic category hub →
- Browse the full library →
- Glossary of terms →
Where researchers source PE-22-28
For researchers studying PE-22-28, third-party suppliers such as Practically Natty Peptides offer research-grade material, third-party tests every batch and provides Certificates of Analysis on request, and ship from the US.
PeptiDex does not maintain a direct supplier listing for this compound. The link above goes to a third-party research-supplier directory.
Frequently asked questions
What is PE-22-28?
PE-22-28, sometimes called mini-spadin, is a synthetic heptapeptide corresponding to residues 22-28 of the endogenous peptide spadin. It is studied in preclinical models of depression and neurogenesis as a proposed inhibitor of the TREK-1 potassium channel.
How does PE-22-28 relate to spadin?
Spadin is a fragment derived from the propeptide of the sorting receptor sortilin, and PE-22-28 is a shortened, optimized fragment of it. Research describes PE-22-28 as among the smallest spadin fragments that retains TREK-1 inhibitory activity, with improved stability over the parent peptide.
What is PE-22-28's proposed mechanism?
PE-22-28 is proposed to act as a TREK-1 channel blocker, a mechanism linked in preclinical work to antidepressant-like effects and increased hippocampal BDNF and neurogenesis. Rodent studies report antidepressant-like behavior emerging within days rather than the weeks typical of SSRIs.
What is the state of human evidence for PE-22-28?
There are no completed, published human clinical trials for PE-22-28. All reported efficacy is from rodent behavioral models, and there is no validated human dose, no human safety data, and no regulatory approval.
Is PE-22-28 an approved drug?
No. PE-22-28 is a preclinical research peptide with no approval in any jurisdiction and is handled strictly as a laboratory research material.
Answers are educational summaries of research-literature context and do not constitute medical advice. See the Research Library, COA guide, and Storage & Handling guide for more.
References
Primary literature indexed in PubMed for PE-22-28. Listing a study records that it exists and is indexed — it is not a claim of efficacy, a therapeutic indication, or an endorsement of its conclusions. Much of this literature is preclinical (in-vitro or animal-model).
- Spadin, a sortilin-derived peptide, targeting rodent TREK-1 channels: a new concept in the antidepressant drug design
- Fighting against depression with TREK-1 blockers: Past and future. A focus on spadin
- Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity
Each reference was checked against its PubMed record on 2026-07-28: the PMID resolves and the title, journal and year match. Where no indexed literature exists for a compound, PeptiDex says so rather than substituting a citation about a different molecule. See the editorial policy.