PE-22-28 is a seven-amino-acid peptide from a French CNRS lab, engineered as a shorter, more stable version of spadin, an endogenous peptide the same group discovered in 2010 with antidepressant-like activity in mice. It works by blocking the TREK-1 potassium channel, and it is entirely a laboratory and mouse-behavioral finding: no human trial of PE-22-28 or spadin has ever been run, and none appears on ClinicalTrials.gov. Its exact amino acid sequence could not be independently confirmed from a primary source for this entry.
What it is
PE-22-28 is a seven-amino-acid peptide developed by a CNRS research group in France (Institut de Pharmacologie Moleculaire et Cellulaire, Universite Cote d’Azur) as a shortened, more stable analogue of spadin, an endogenous 17-residue peptide the same group first described in 2010 as a TREK-1 potassium channel inhibitor with antidepressant activity in mice. PE-22-28 is not itself spadin; it is a designed fragment built from spadin’s own blood-degradation products, intended to fix spadin’s short duration of action.
TREK-1 is a two-pore-domain potassium channel that dampens neuronal excitability; blocking it is the proposed mechanism behind the antidepressant-like effect reported for this peptide class in mice. This is an entirely preclinical mechanism, worked out in patch-clamp electrophysiology on cultured cells and in mouse behavioural models, not in any human tissue or human trial.
Potential benefits and research applications
Antidepressant-like effect, shown only in mouse behavioral screening assays
In the 2017 paper introducing it, PE-22-28 reduced immobility time in the mouse forced swimming test and reduced latency to eat in the novelty-suppressed feeding test after four days of dosing, both standard antidepressant-screening assays used to flag candidate compounds for further development, not to confirm a clinical antidepressant effect.
Evidence: has been shown in mouse behavioral assays (Tier 3, published animal evidence); has not been established in any human trial, and no such trial exists on ClinicalTrials.gov.
Neurogenesis and synaptogenesis markers, demonstrated only in cultured cells
The same study reported measurable neurogenesis after four days of treatment and increased PSD-95 (a synaptogenesis marker) expression in cultured mouse cortical neurons, offered as a possible mechanistic explanation for the behavioral findings above.
Evidence: is being investigated at the laboratory/cell-culture level (Tier 4); has not been established in any living animal’s brain tissue or in any human.
Improved potency and duration over spadin, a pharmacology finding rather than a clinical benefit
PE-22-28 inhibited the human TREK-1 channel expressed in HEK293 cells roughly 300- to 500-fold more potently than spadin in the same assay, with an effective duration extended to about 23 hours versus about 7 hours for spadin. This describes the molecule’s laboratory pharmacology, not a demonstrated advantage in a living organism, let alone a human being.
Evidence: is a laboratory/mechanistic finding (Tier 4); has not been established as a clinical or even in-vivo human advantage.
What has actually been tested
The 2017 paper introducing PE-22-28 reported that it inhibited the human TREK-1 channel expressed in HEK293 cells with an IC50 of 0.12 nanomolar, roughly 300- to 500-fold more potent than spadin itself in the same assay (spadin: 40-60 nanomolar). In mice, PE-22-28 and its derivatives reduced immobility time in the forced swimming test, a standard antidepressant-screening assay, and reduced the latency to eat in the novelty-suppressed feeding test after four days of sub-chronic dosing. The same paper reported that PE-22-28 induced measurable neurogenesis after four days of treatment and increased a marker of synaptogenesis (PSD-95 expression) in cultured mouse cortical neurons, with its effective duration of action extended to about 23 hours, compared with about 7 hours for spadin.
No human trial of PE-22-28, or of spadin, appears on ClinicalTrials.gov, and no human pharmacokinetic, safety or efficacy study was located in this search. Every finding described above is a mouse behavioural result, a cultured human cell line’s channel response, or a cultured mouse neuron’s marker expression, not a demonstration in a living human being.
What is not known
Whether the antidepressant-like effect seen in mouse forced-swimming and novelty-suppressed-feeding assays, which are screening tools with known limits for predicting real antidepressant efficacy in people, translates into an actual antidepressant effect in a human being. No human trial has tested this.
Human pharmacokinetics, human dosing, and human safety at any level. No such data exists for PE-22-28 in the sources reviewed for this entry.
The peptide’s exact published amino acid sequence was not independently confirmed from a primary source for this entry and is not printed here; readers should treat any specific sequence given elsewhere for PE-22-28 with the same caution this entry applies to unconfirmed identifiers generally.
Frequently asked questions
What is PE-22-28?
It is a seven-amino-acid peptide from a French CNRS lab, a shortened and more stable analogue of spadin, designed to inhibit the TREK-1 potassium channel. It has never been dosed in a human being in any trial located for this entry.
How does PE-22-28 work?
It blocks the TREK-1 potassium channel, which dampens neuronal excitability; blocking it is the proposed mechanism behind the antidepressant-like effect reported in mice. This mechanism has been worked out only in cultured cells and mouse models.
What dosage has been studied in humans?
No established or reliably sourced human dosing information was identified. No human trial of PE-22-28 exists.
What dosage commonly circulates online?
Community material describes 250 to 500 micrograms subcutaneously, once daily. This figure has no published animal or human study behind it that this entry could locate; the primary literature reports no subcutaneous dose at all.
Has PE-22-28 been studied in humans?
No. No human trial of PE-22-28 or of its parent peptide spadin appears on ClinicalTrials.gov, and none was located anywhere else for this entry.
Is PE-22-28 approved for use?
No. It is not approved for human use in any jurisdiction.
What routes of administration are reported?
The 2017 study used channel assays in cultured cells and behavioral testing in mice; a specific administration route for the mouse studies was not detailed in the source reviewed. Community-reported use describes subcutaneous injection.
Does PE-22-28 treat depression?
This has not been established. The antidepressant-like effect is limited to standard mouse screening assays, which are used to flag candidates for further study, not to confirm a clinical effect in people.
What side effects have been reported?
No human safety or adverse-event data exists, because no human trial of PE-22-28 has been conducted.
What remains unknown about PE-22-28?
Whether its mouse antidepressant-screening results would translate to a human antidepressant effect; its human pharmacokinetics, dosing and safety, none of which exist; and a confirmed, primary-source amino acid sequence, which this entry could not verify.
Bottom line
PE-22-28 is a genuinely interesting piece of French pharmacology, a stabilised, far more potent successor to the antidepressant-candidate peptide spadin, but it is entirely a preclinical finding. Every result comes from cultured cells or mouse behavioral assays; no human trial of PE-22-28 or spadin has ever been run, and none is registered on ClinicalTrials.gov. The doses circulating in research-peptide communities have no study of any kind, in any species, behind them.