PE 22-28 Peptide: Research, Mechanism and Safety
PE 22-28 peptide is a 7 amino acid spadin analog studied as a possible antidepressant. In 2017 mouse tests it cut giving-up time in the forced swim test, and its effect lasted up to 23 hours, against 7 hours for spadin.
It works by blocking TREK-1, a channel on nerve cells, and in cells it blocked human TREK-1 at 0.12 nM, against 40 to 60 nM for spadin. It has not been tested in people. The only dose on record is 3 µg/kg in mice, so there is no human protocol.
Short answer
- What does PE 22-28 do?
- It blocks the TREK-1 potassium channel in lab cells.
- What was it tested for?
- Depression-like behavior in mice, in a 2017 study.
- Is there a human dose?
- No. The only dose on record is 3 µg/kg in mice.
Where does PE 22-28 come from?
It was designed from the pieces spadin breaks into in blood. Spadin itself is cut from a protein called sortilin, also known as NTSR3.
A 2010 mouse study showed antidepressant effects for spadin, acting through TREK-1. The 2017 study then built a 7 amino acid peptide from spadin's blood breakdown products and named it PE 22-28. A 2019 review calls it the shortest piece of spadin that still showed antidepressant activity in animal tests.
You will also see it written as PE-22-28. Both names mean the same peptide.
Sources: Spadin, a sortilin-derived peptide, targeting rodent TREK-1 channels: a new concept in the antidepressant drug design (13 April 2010), PubMed 20405001: spadin origin and mouse study; Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity (12 September 2017), PubMed 28955242: design of PE 22-28, TREK-1 block and mouse tests; Role of TREK-1 in Health and Disease, Focus on the Central Nervous System (11 April 2019), Europe PMC PMC6470294: PE 22-28 as the shortest active spadin piece
How does PE 22-28 compare with spadin?
It blocked TREK-1 far more strongly and its effect lasted longer, in cells and mice. The 2017 study reports these figures, including the animal doses it gave to mice:
| Measure | PE 22-28 | Spadin |
|---|---|---|
| TREK-1 block, IC50 in human TREK-1 cells | 0.12 nM | 40 to 60 nM |
| How long the effect lasted in animals | Up to 23 h | 7 h |
| Mouse dose in the 4 day feeding test (animal dose) | 3 µg/kg | 100 µg/kg |
A lower IC50 means a stronger blocker. Disclaimer: the 3 µg/kg and 100 µg/kg figures are animal doses from a mouse test, not human doses and not a recommendation. Mouse doses do not convert to people, and any decision about a compound belongs with a licensed clinician.
Sources: Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity (12 September 2017), PubMed 28955242: design of PE 22-28, TREK-1 block and mouse tests; Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity (12 September 2017), Europe PMC PMC5601071: full text, mouse doses and hERG result
What did the mouse tests show?
In the 2017 study, mice given PE 22-28 behaved the way mice on antidepressants do in standard tests. These are animal results only.
- Forced swim test: mice given PE 22-28 or its relatives spent less time still.
- New setting feeding test: after 4 days of PE 22-28, mice started eating sooner in an unfamiliar place.
- Brain cells in a dish: PE 22-28 raised PSD-95, a marker of new nerve connections, in mouse cortical neurons.
A 2019 review sums up the analogs the same way: stronger TREK-1 blocking, better antidepressant activity in animals and longer action in the body.
Sources: Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity (12 September 2017), PubMed 28955242: design of PE 22-28, TREK-1 block and mouse tests; Fighting against depression with TREK-1 blockers: Past and future. A focus on spadin (February 2019), PubMed 30291907: review of spadin analogs and fluoxetine
What does TREK-1 have to do with mood?
TREK-1 is a potassium channel on nerve cells, and blocking it is one route researchers study for depression. A 2019 review notes that fluoxetine, a TREK-1 blocker, has proven benefit for depression in the clinic.
That finding is about fluoxetine, not PE 22-28. No study measured mood, focus or mental clarity in people taking PE 22-28. For peptides studied for the brain, see peptides for brain function and the Semax profile.
Is PE 22-28 safe?
No one knows, because it has never been tested in people. Two lab findings touch on safety, and neither one settles it.
First, in the 2017 cell tests, PE 22-28 and its relatives had no effect on hERG channels, which carry a key heart current. Second, researchers worried that blocking TREK-1 could cause side effects. A 2012 study found the parent peptide spadin did not interfere with pain, epilepsy or ischemia. That study used spadin, not PE 22-28.
The FDA page on risky compounding ingredients does not list PE 22-28 or spadin, so no regulator has reviewed it.
Sources: Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity (12 September 2017), Europe PMC PMC5601071: full text, mouse doses and hERG result; Spadin as a new antidepressant: absence of TREK-1-related side effects (January 2012), PubMed 21807005: spadin side effect study
How is PE 22-28 different from Selank?
They act on different targets, and only Selank has been studied in people. PE 22-28 blocks TREK-1, while a 2018 review says Selank acts on GABA receptors in lab tests.
A 2014 Russian study compared Selank with the drug phenazepam in 60 patients with anxiety disorders. No such study exists for PE 22-28. For more on Selank, see the Selank profile.
Sources: Peptide-based Anxiolytics: The Molecular Aspects of Heptapeptide Selank Biological Activity (2018), PubMed 30255741: Selank and GABA receptors; A comparison of the anxiolytic effect and tolerability of selank and phenazepam in the treatment of anxiety disorders (2014), PubMed 25176261: Selank study in 60 patients
Common Questions
What is PE 22-28 used for?+
In research, PE 22-28 is used to study depression in mice. It was designed as a shorter, stronger version of spadin, a peptide that blocks the TREK-1 channel. It has no approved medical use, and it has not been tested in people.
Is PE 22-28 safe?+
No one knows, because it has never been tested in people. In the 2017 cell tests, it did not affect hERG channels, which carry a heart current. In a 2012 study, the parent peptide spadin did not interfere with pain, epilepsy or ischemia. Neither result shows PE 22-28 is safe for a person.
What is the PE 22-28 peptide protocol?+
There is no human protocol. The only dose found is an animal dose: in the 2017 study, mice got 3 micrograms per kilogram for 4 days in one test. That figure does not convert to a human dose.
What are the differences between the PE-22-28 peptide and Selank peptides?+
Both are 7 amino acid peptides, but they are reported to act on different targets. PE 22-28 blocks the TREK-1 channel in lab tests. Selank acts on GABA receptors in lab tests. Selank has a 2014 human study in 60 patients with anxiety disorders. PE 22-28 has no human study.
What is the best peptide for mental clarity?+
The PE 22-28 research cannot answer that. It has only mouse and cell data, and none of it measured mental clarity in people. Our guide to peptides for brain function gives an overview.
What is the strongest peptide for weight loss?+
PE 22-28 is not a weight loss peptide. No study found measured weight loss with it.
What are the top 3 peptides to take?+
This page does not rank peptides or say what to take. For PE 22-28 itself, the record is cell and mouse studies only.
What are the reviews of the PE-22-28 peptide?+
User reviews are not research, so this page does not report them. The published record is cell and mouse studies only.
Sources: Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity (12 September 2017), PubMed 28955242: design of PE 22-28, TREK-1 block and mouse tests; Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity (12 September 2017), Europe PMC PMC5601071: full text, mouse doses and hERG result; Spadin as a new antidepressant: absence of TREK-1-related side effects (January 2012), PubMed 21807005: spadin side effect study; A comparison of the anxiolytic effect and tolerability of selank and phenazepam in the treatment of anxiety disorders (2014), PubMed 25176261: Selank study in 60 patients; Peptide-based Anxiolytics: The Molecular Aspects of Heptapeptide Selank Biological Activity (2018), PubMed 30255741: Selank and GABA receptors
Related reading
This guide is for educational purposes only and is not medical advice. It describes what published cell and mouse research reports about PE 22-28. It is not an endorsement or an instruction to use any compound. PE 22-28 is a research compound that is not approved for human use. Talk to a qualified healthcare professional before making any decision about your health.