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Lexicon
Cognition

PE 22-28

A shortened spadin analog that blocks the TREK-1 channel, an experimental antidepressant approach from basic research.

2 min read 8 sources

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Vial with white powder, a blue cap and a black TPD label for PE 22-28 on a white podium, next to it a chain of blue and white glass spheres as a molecule model in a bright lab
Preclinical · not approved

Summary

At a glance

Sources checked on 26 Oct 2026

Length
7 amino acids

shortened from spadin, which has 17 amino acids2

TREK-1 inhibition (IC50)
0.12 nM

in human cells with TREK-1, spadin needed 40 to 60 nM2

Duration of action in mice
~23 hours

up to 23 hours instead of 7 hours with spadin2

Until effect in mice
4 days

after 4 days of dosing behaviour as under antidepressants and new nerve cells2

Human trials in the registry
0 trials

no trial with PE 22-28 or spadin on ClinicalTrials.gov, as of 26 Oct 20267

  • PE 22-28 is a peptide of seven amino acids, shortened from spadin. Spadin forms in the body as a fragment during the maturation of the protein sortilin.81
  • Both block the potassium channel TREK-1. Mice without TREK-1 behaved as if on antidepressants in five models. The research builds on that.31
  • In human cells with TREK-1, PE 22-28 inhibited the channel much more strongly than spadin. In mice it acted for up to 23 instead of 7 hours.2
  • After four days of dosing mice showed fewer signs of depression in behaviour tests. New nerve cells formed and there was more synapse protein.2
  • ClinicalTrials.gov lists no human trial of PE 22-28 (as of October 2026). Everything here is preclinical research, not a recommendation.7
Profile

Updated May 2026

Class
Spadin analog

TREK-1 blocker

Use
Subcutaneous

in mcg

Half-life
short
Status
Preclinical

no human data

Sizes
10 mg

1 size in the shop

Contents 16 sections
  1. At a glance
  2. What is PE 22-28?
  3. How it works
  4. What you need
  5. Reconstitution
  6. Dosing
  7. Injection
  8. What the research shows
  9. Research status
  10. Side effects
  11. Practice
  12. Storage
  13. Related compounds
  14. FAQ
  15. Glossary
  16. Sources

What is PE 22-28?

PE 22-28 is a shortened analog of spadin, an endogenous peptide. It blocks the potassium channel TREK-1, which plays a role in mood and depression. The idea: a fast-acting antidepressant principle that works differently from classic agents.

Up front: this is basic research, there is no human data.

Comparison

Other peptides focused on the brain

Rough classification by origin. Tap a card to open its entry.

Spadin derivative, TREK-1 blocker PE 22-28 TREK-1
Tuftsin derivative Selank ACTH(4-7) derivative Semax CNTF derivative P21

The origin of the other peptides is described in their lexicon entries. Only for PE 22-28 the target is shown here.

How it works

The TREK-1 channel dampens the activity of certain nerve cells. Blocking it raises their excitability, which in animal models was associated with a fast antidepressant effect and increased formation of nerve cells. PE 22-28 is an optimized, more stable version of spadin.

Where it acts

Where PE 22-28 acted in experiments

Tap a point or a card. All from cell and animal studies.

  1. Brain

    TREK-1 inhibited, in mice fewer signs of depression and new nerve cells2

    TREK-1

Known targets2

Compound PubChem CID 165437303: one described target, Channel blocker, measured in human cells with TREK-1.

Potassium channel TREK-1 (K2P2.1)
Gene
KCNK2
UniProt
O95069
ChEMBL
CHEMBL2321615
Action
Channel blocker, measured in human cells with TREK-1
Glowing glass nerve cell with small pores in its wall, two blue molecules docking on, further nerve cells beside it
PE 22-28 blocks the TREK-1 channel, in animal models this was linked to antidepressant effects. Symbolic image.

What you need

Supplies

2 things, numbered as in the picture

Tick off what you already have. Vial and BAC water are our real shop photos at the same size.

PE 22-28 vial and bacteriostatic water at the same size with the black TPD label, next to two U-100 insulin syringes, two alcohol swabs and a sharps container with a blue lid

  1. PE 22-28 vial

    The PE-22-28 vial (lyophilized powder).

    In the shop

  2. Water and supplies

    Bacteriostatic water, U-100 insulin syringes, alcohol swabs.

    In the shop

Reconstitution

Use the peptide calculator. A 10mg vial with 3ml water gives about 3333mcg per ml, 100mcg is then 3 units on the U-100 syringe. Just add the water to the vial and let it dissolve.

Step by step

Dissolving the powder

Four steps, the same for every vial size.

  1. 1Wipe the cap

    Clean the rubber stopper with an alcohol swab.

  2. 2Add BAC water

    Just add it, it does not matter if it hits the powder directly.

  3. 3Swirl or shake

    Until everything has dissolved, both are fine.

  4. 4Draw up

    With the U-100 insulin syringe.

Less water higher concentration fewer units on the syringe Example: 10 mg + 2 ml = 5 mg/ml

Dosing

Dosing

Dosing, titration and syringe

Loading the dosing information …

  • Getting started and stepping up, drawn as a staircase
  • Units on the U-100 syringe for every step
  • How long one vial lasts

Injection

The injection is subcutaneous, into the fat layer under the skin. Common spots are the abdomen (keep about two finger-widths clear of the navel), the front and the inner side of the thigh, or the back of the upper arm.

The short version:

Injection

Where and at what angle

Pick a spot or switch the angle. Subcutaneous means: into the fat layer, not the muscle.

Rotate the spot each time, never the same one twice in a row.

90°More fat under the skin

Rule of thumb: where there is more fat under the skin, insert straight at 90 degrees. In lean people with little fat, 45 degrees, so the needle stays in the fat layer. Simplified diagram.

  1. Clean the spot with an alcohol swab and let it dry

  2. Pinch up a small fold of skin

  3. Insert the needle: at 90 degrees where there is more fat under the skin, at 45 degrees in lean people with little fat

  4. Inject slowly, wait a moment, then withdraw

  5. Put the needle straight into the sharps container

Rotate the site each time so the tissue does not get irritated. Never the same spot twice in a row.

What the research shows

Spadinwas described as a TREK-1 blocker with an antidepressant profile (Mazella, 2010). Shortened analogs like PE 22-28 showed better channel inhibition, higher stability and antidepressant activity in animal models (Djillani, 2017). All of this is preclinical, human studies are missing.

Study results

What the trials measured

Interactive: switch tabs, tap points, show or hide arms. Arms are named relative to each other, no dosing advice.

How long the effect lasted2

Duration of action in mice in hours

Antidepressant effect2 Mice, values according to the abstract
Spadin (parent peptide) 7 h
PE 22-28 23 h up to

Spadin no longer acted after 7 hours, PE 22-28 and its derivatives for up to 23 hours. Measured in mice, not studied in humans.

Glass shelves with petri dishes, a glass brain on the middle shelf, lit from behind by evening light
All preclinical, human studies are missing. Symbolic image.

Research status

Where the research stands

So far PE 22-28 and spadin have been studied in cells and mice, mainly by one group in Valbonne (France). As of 26 Oct 2026. 7

  1. Preclinical Cell assays and behaviour models in mice
  2. Phase 1 no registered trial
  3. Phase 2 no registered trial
  4. Phase 3 no registered trial
  5. Approval not yet
Not approved and no registered human trial. PE 22-28 has only been studied preclinically so far.7

So far there is no registered trial in humans. 7

Side effects

  • Solid human data are missing, so little is known about side effects.
  • Local reactions at the injection site.
  • Reaching into mood systems is not harmless, particular caution is warranted here.

Practice

  • Clearly experimental, keep expectations low.
  • With pre-existing mental health risk, leave it alone.
A cup of tea, a light blue notebook and a green plant on a sunny windowsill overlooking the water
Clearly experimental, stay away from it if you have a history of mental health problems. Symbolic image.

Storage

Before mixing the powder is robust, normal room temperature (around 20 to 25 degrees) is fine, ideally kept in the dark. After mixing, keep in the fridge (2 to 8 degrees), do not freeze. It stays good there for at least 4 to 6 months with barely any loss of potency, in practice considerably longer. Swirl or shake to mix, both are fine.

Shelf life

How long it keeps

Undissolved (powder) Room temperature, around 20 to 25 degrees, dark

Robust, no fridge needed.

Dissolved (mixed) Fridge, 2 to 8 degrees, do not freeze

At least 4 to 6 months with barely any loss of potency.

  • Keep it dark
  • Dissolved: 2 to 8 degrees
  • Note the mixing date on the vial
Nine vials with white powder and blue caps in the door shelf of a bright fridge
Powder dark at room temperature, once dissolved into the fridge (2 to 8 degrees), stable there for at least 4 to 6 months. Symbolic image.

Related

Related compounds

A different path: all in the TPD lexicon.

PE 22-28
Selank Different peptide focused on mood and anxiety Semax Different short peptide focused on the brain P21 Different peptide, new nerve cells in mice DSIP Different peptide focused on sleep Pinealon Short peptide from the Khavinson programme, brain

FAQ

Common questions about PE 22-28

Short answers, each backed by the sources below.

Is PE 22-28 approved or studied in humans?

No. There is no approval and as of 26 October 2026 ClinicalTrials.gov lists no trial with PE 22-28 or spadin. All data come from cell experiments and mice.7

Where does PE 22-28 come from?

From spadin, a peptide of 17 amino acids that forms during the maturation of the protein sortilin. In mice spadin stopped working after 7 hours. From its breakdown fragments the group designed the shorter PE 22-28 with seven amino acids.12

What does TREK-1 have to do with mood?

TREK-1 is a potassium channel that slows nerve cells down and is partly controlled by serotonin. Mice without TREK-1 behaved as if on antidepressants in five models, with stronger serotonin signalling and less corticosterone under stress. That is the basis for the idea of blocking the channel with a peptide.3

What did the mouse studies show?

With PE 22-28 mice stayed motionless for less time in the swim test, a common measure of antidepressant effect. After four days of dosing they approached food in a new environment sooner. New nerve cells formed as well. In nerve cells in culture the synapse protein PSD-95 rose.2

Has a shorter spadin also been studied after a stroke?

Yes, in mice. A shortened spadin analogue (mini-spadin) protected against weight loss, nerve cell loss and signs of depression after an artificially induced stroke. At a low amount it activated TREK-1, at a higher amount it inhibited the channel.5

Which side effects are known?

There are no human data for PE 22-28. For the parent peptide spadin the group found no effect on heart, blood pressure, pain perception, seizure threshold or blood sugar in mice. That cannot be transferred to humans. An intervention in mood is never harmless.47

Glossary

Terms explained briefly

Dotted words in the text open these explanations directly.

Hippocampus
Brain region for learning and memory, also important for mood.
IC50
The concentration at which a substance inhibits its target by half. The smaller it is, the stronger the effect.
Lyophilisate
Freeze-dried powder. Without water a peptide keeps much longer.
Neurogenesis
Formation of new nerve cells. In adults it mainly takes place in the hippocampus.
Potassium channel
A pore in the cell membrane through which potassium flows. It controls how easily a nerve cell fires a signal.
Preclinical
Research before first use in humans, in cell cultures and animal models. Results cannot be transferred directly to humans.
Sortilin
Protein in the cell membrane, also called neurotensin receptor 3. During its maturation a piece is cut off. Spadin comes from it.
Spadin
Endogenous peptide of 17 amino acids that forms during the maturation of sortilin and blocks TREK-1. Parent form of PE 22-28.
Subcutaneous
Into the fat layer just under the skin.
TREK-1
Potassium channel in the membrane of nerve cells. When it is open the cells are harder to excite. Gene KCNK2.

Evidence

Sources

Show all 8 sourcesHide sources 6 Studies1 Trial registry1 Database checked 26 Oct 2026

Studies

  1. Spadin from sortilin blocks TREK-1 (cells and mice)

    Mazella et al., PLoS Biology, 2010

    DOI 10.1371/journal.pbio.1000355 PMID 20405001
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed, PMC (Volltext)
  2. Shortened spadin forms such as PE 22-28: stronger and longer acting (cells and mice)

    Djillani et al., Frontiers in Pharmacology, 2017

    DOI 10.3389/fphar.2017.00643 PMID 28955242
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed, PMC (Volltext)
  3. Mice without TREK-1 behave as if on antidepressants

    Heurteaux et al., Nature Neuroscience, 2006

    DOI 10.1038/nn1749 PMID 16906152
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  4. Spadin without typical TREK-1 side effects in mice

    Moha ou Maati et al., Neuropharmacology, 2012

    DOI 10.1016/j.neuropharm.2011.07.019 PMID 21807005
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  5. Mini-spadin after stroke in mice

    Pietri et al., Neuropharmacology, 2019

    DOI 10.1016/j.neuropharm.2019.107715 PMID 31325429
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  6. Review of TREK-1 blockers and spadin

    Djillani et al., Pharmacology and Therapeutics, 2019

    DOI 10.1016/j.pharmthera.2018.10.003 PMID 30291907
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed

Trial registry

  1. Search on ClinicalTrials.gov (no trial with PE 22-28)

    ClinicalTrials.gov, U.S. National Library of Medicine

    Checked 26 Oct 2026 via ClinicalTrials.gov API v2

Database

  1. Structure of PE 22-28 in PubChem

    PubChem, U.S. National Library of Medicine (CID 165437303)

    Checked 26 Oct 2026 via PubChem

In the shop

PE 22-28 in the catalog

Sizes, prices and shipping times are on the product page.

To the product