PE-22-28
Spadin Analog Nootropic
aka Spadin · PE 22-28 · TREK-1 blocker
A TREK-1 channel blocker researched for rapid antidepressant and pro-cognitive effects in animal models.
Sequence
GVSWGLR
Gly-Val-Ser-Trp-Gly-Leu-Arg
Mechanism of action
PE-22-28 works by blocking the TREK-1 potassium channels, which are involved in regulating neuronal excitability and mood. By inhibiting these channels, PE-22-28 may enhance neurotransmitter release, particularly serotonin, leading to rapid antidepressant effects. This action can also improve cognitive function by modulating synaptic plasticity.
What the evidence actually shows
There are currently no published human clinical trials for PE-22-28. Existing evidence is primarily from animal studies, which suggest rapid antidepressant and cognitive-enhancing effects. Human trials are needed to confirm efficacy and safety.
Regulatory status
PE-22-28 is not approved for medical use in the UK and is considered a research compound.
Source ↗Pharmacokinetics
Dosing — what backs each figure
PE-22-28 is a shortened spadin analogue and a TREK-1 blocker studied only in mice, where 4-day courses of 3-4 ug/kg intraperitoneally (or 1 mg/kg by gavage) produced antidepressant-like behavioural effects. There is no human trial, no human dose and no established route.
PE 22-28 given as 4-day sub-chronic treatment at 3-4 ug/kg (and, in the same figure series, 100 ug/kg) by intraperitoneal injection, or 1.0 mg/kg by oral gavage; assessed in forced swim, novelty-suppressed feeding and learned helplessness tests
mouse · intraperitoneal and oral gavage · PMID 28955242
Animal doses do not convert to human doses by body weight alone. Route matters too — a compound dosed intraperitoneally in mice tells you little about subcutaneous use.
- Dose
- 200-500 mcg/day
- Frequency
- Daily
Why this isn't evidence
PE 22-28 has never been administered to a human at any dose, and the mouse work uses weight-based microgram-per-kilogram intraperitoneal dosing or milligram-per-kilogram gavage, neither of which yields a fixed 200-500 mcg/day human figure.
This figure is shown because it is what circulates and what people search for — not because it is supported. Cycle lengths in particular tend to be convention copied between compounds rather than anything derived from a compound's own pharmacokinetics.
Handling and storage
Safety
- ·Mild headache
- ·Nausea
- ·Seizures
- ·Severe liver impairment
- ·Pregnancy
- ·SSRIs: Potential additive serotonergic effects
Reported combinations
- ·Omega-3 fatty acids
- ·Benzodiazepines: May counteract cognitive benefits
Combination claims in this dataset are largely unsourced and should be treated as folk knowledge until a citation appears beside them.
References (2)
- Djillani A, Pietri M, Moreno S, Heurteaux C, Mazella J, Borsotto M. (2017) Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity ↗Front PharmacolPMID 28955242DOI
Describes the design of the 7-amino-acid peptide PE 22-28 from spadin degradation products. Reports TREK-1 inhibition with IC50 of 0.12 nM versus 40-60 nM for spadin, duration of action extended to about 23 hours versus about 7 hours, and reduced immobility time in the mouse forced swim test at 3.2-4.0 micrograms/kg. Mouse and in vitro study.
- Mazella J, Petrault O, Lucas G, Deval E, Beraud-Dufour S, Gandin C, et al. (2010) Spadin, a sortilin-derived peptide, targeting rodent TREK-1 channels: a new concept in the antidepressant drug design ↗PLoS BiolPMID 20405001DOI
Original description of spadin (the parent peptide of PE 22-28) as a TREK-1 blocking antidepressant candidate in mice. Rodent study.
Data provenance
Chemistry and citations on this page were checked against primary sources on 2026-08-14. Values that could not be verified were left blank rather than filled with a plausible guess.
Could not verify
storage.lyophilized, storage.reconstituted, storage.lightSensitive, reconstitution.solvent, regulatory.wada