PE-22-28
Mood, Neurogenesis
No published human pharmacokinetics; preclinical work only.
In short
- A spadin-derived peptide that blocks the TREK-1 potassium channel, a validated antidepressant target.
- TREK-1 knockout mice show a depression-resistant phenotype, which is what makes the target credible.
- Rodent studies report antidepressant-like effects within days rather than weeks — the profile that makes rapid-acting antidepressants interesting.
- No human trial of any kind has been published.
- Research compound only.
Structure
A 7-amino-acid peptide derived from spadin. PubChem has no entry under this research-market name; peptides are represented by sequence rather than a structure diagram.
How it works
TREK-1 is a two-pore-domain potassium channel expressed in brain regions involved in mood regulation. Mice lacking TREK-1 show a phenotype resembling antidepressant treatment, which established the channel as a target.
Spadin is an endogenous peptide derived from the propeptide of sortilin that blocks TREK-1. PE-22-28 is a shortened, more stable analogue of the active spadin sequence.
Blocking TREK-1 increases serotonergic neuron excitability, and the rapid onset reported in rodents is attributed to this acting downstream of the slow adaptations that conventional antidepressants require.
What the research shows
Rodent studies report antidepressant-like effects in behavioural despair models within four days, alongside increased hippocampal neurogenesis and synaptogenesis.
The target validation through TREK-1 knockout mice is genuinely strong preclinical evidence.
No human study has been conducted. Nothing is known about whether it works, is safe, or even reaches the brain in people.
Dosing in the literature
Figures below are quoted from published studies, with the species or population they were measured in. They are records of what was studied, not recommendations.
| Studied in | Amount | Route | Source |
|---|---|---|---|
| Mouse — antidepressant behavioural models | Microgram-per-kilogram ranges; see source | intraperitoneal or intranasal | PubMed |
Commonly reported ranges
These are amounts people report using. They are not from any study, have not been evaluated for safety, and are reproduced here only because they circulate widely and are better seen alongside the evidence than instead of it.
| Reported by | Amount | Route |
|---|---|---|
| Commonly reported | 200–500 µg daily | intranasal or subcutaneous |
No published human pharmacokinetic study establishes a dose, interval, or duration for this compound. Community figures below have no trial behind them and are reports of practice, not evidence. No human has been dosed under study. Community protocols are improvised entirely from rodent work.
Handling and storage
Supplied as a lyophilised powder requiring reconstitution with bacteriostatic water. The powder is comparatively stable; once reconstituted it is refrigerated and used within weeks. Track the date you reconstitute each vial — the Inventory section does this, and it is the difference between knowing a vial is three weeks old and guessing.
Intranasal or subcutaneous use is described in community practice. Some rodent work used intranasal administration on a nose-to-brain rationale.
Side effects
No human safety data exists. No toxicology has been published.
Rodent studies did not report significant adverse effects, but they were efficacy studies rather than safety studies.
TREK-1 is expressed outside the brain, including in cardiac and vascular tissue, so systemic channel blockade is not CNS-exclusive. What that means in a human is unknown.
Combinations
No interaction data. Combining with serotonergic antidepressants would act on overlapping pathways and is entirely unstudied.
Research status
Developed from work by Marc Borsotto, Catherine Heurteaux and colleagues in France on spadin and TREK-1.
The preclinical science is legitimate and published in reputable journals. No clinical development has been announced.
Legal status
Not approved in any jurisdiction. Sold for research use only.
WADA status
Not specifically named on the Prohibited List. Falls under WADA class S0, which prohibits any pharmacological substance not currently approved by any governmental regulatory health authority for human therapeutic use. Treat it as prohibited in sport.
Conclusion
PE-22-28 has one of the better-validated preclinical targets in this library, supported by knockout-mouse genetics rather than just pharmacology.
It also has no human data whatsoever. Strong target validation in mice is where most failed antidepressant programmes began, not where they ended.
Sources
Track your own PE-22-28 protocol
Peppers logs your doses, models your levels from this half-life, tracks your vials and tells you when you will run out. Free on iPhone.
Reference and educational information only. Not medical advice. Nothing here diagnoses, treats, or prescribes, and nothing here is a recommendation to use any compound. The compounds described are research chemicals and are not approved for human consumption. Legal and anti-doping status change — the review date above is when these claims were last checked. Talk to a qualified clinician about anything you intend to take.