PE 22-28 Peptide: What the Mouse Studies Show

PE 22-28 is a seven-amino-acid peptide that blocks TREK-1, a potassium channel linked to mood in mice. In a 2017 mouse study, one injection cut immobility in a forced swim test 30 minutes later. No human has been given it in a published trial, and it is not FDA-approved.

What Is PE 22-28?

PE 22-28 is the peptide Gly-Val-Ser-Trp-Gly-Leu-Arg (GVSWGLR), with a molecular weight of about 774. It is a short fragment of spadin, a longer peptide made when the protein sortilin matures inside cells. The numbers in the name are positions in the parent sequence. They are not a count of amino acids.

Does PE 22-28 Work For Depression?

Not in people. The mouse results come from one 2017 paper by the research group that developed spadin.

In cells, PE 22-28 blocked human TREK-1 at 0.12 nM. Spadin needed 40 to 60 nM. That makes PE 22-28 about 330 to 500 times more potent at the channel, in cells.

In mice:

• Forced swim test, 30 minutes after one injection of 3.0 µg/kg: immobility fell to 98.1 seconds from 164.9 seconds in mice given corticosterone (10 mice per group). In mice without corticosterone it fell to 91.8 seconds from 161.7.
• Four days of dosing: the hippocampus held more new cells (BrdU count 1,736 against 899 on saline, 5 mice per group). A synapse marker, PSD-95, rose in cultured mouse neurons.
• Four days of treatment also produced antidepressant-like effects in behavioral tests.

Why Is TREK-1 A Target?

In 2006, a team led by Catherine Heurteaux deleted the TREK-1 gene in mice. The mice resisted depression-like behavior in five different models (Nature Neuroscience). The authors suggested TREK-1 could be a target for new antidepressants.

What About Stroke And Diabetes?

A 2019 mouse study gave a sortilin-derived peptide called mini-spadin after a stroke. A very low dose (0.03 µg/kg) increased TREK-1 activity. A higher dose (3 µg/kg) inhibited it and prevented depression-like behavior. Treated mice also lost less weight, had slower loss of dopamine neurons and had better motor and cognitive scores. The abstract does not say whether mini-spadin has the same sequence as PE 22-28.

A 2021 study found that sortilin-derived peptides, including mini-spadin, protected insulin-producing beta cells from interleukin-1β-induced death through CREB signaling. Mini-spadin also promoted beta-cell proliferation. This is cell work.

What Has Not Been Tested?

• Any human. No clinical trial of PE 22-28 has been published.
• BDNF. It was measured for spadin in earlier work, not for PE 22-28.
• Heart, seizure and pain effects in animals. The 2017 paper did not assess them.
• Nasal delivery. The studies on this page used injection and gavage in mice.
• Anxiety or focus effects. No data exist.

Is PE 22-28 Safe?

No human safety data exist. In cells, the analogs did not affect the hERG heart channel at 10 µM, and PE 22-28 did not affect four related channels (TREK-2, TRAAK, TRESK and TASK-1) at 100 nM.

The authors did not test heart, seizure or pain effects in mice. They expect none, based on earlier spadin work. That is an expectation, not a result.

TREK-1 blockers are proposed to raise serotonin neuron activity. If you take an SSRI, SNRI, MAOI or another serotonin drug, talk to your prescriber first. Serotonin syndrome is a theoretical risk when drugs like these are combined. If you are dealing with depression, talk to a clinician.

What Is The Dose?

No human dose exists. The mouse studies used 3.0 µg/kg by injection. That cannot be converted into a safe human dose. This page does not list doses, cycles or prices.

PE 22-28 Vs Ketamine

Is PE 22-28 Legal Or FDA-Approved?

• Not FDA-approved for any use.
• Not on FDA’s Category 2 list, and not among the seven peptides its advisory committee reviewed in July 2026.
• Sold as a “research chemical.” FDA has said a “research use only” label does not make a product legal to sell for human use.
• Athletes: WADA’s class S0 bans non-approved substances at all times.

How Do You Check A PE 22-28 Vial?

• A lab report that matches the lot number on your vial.
• The sequence GVSWGLR and a mass near 774 on the report.
• An independent lab you can look up.

Skip any seller with no lab report or an FDA warning letter. See our peptide vendors ranked by lab-report evidence and our fake peptide vendors list.

Bottom Line

PE 22-28 is an interesting idea with mouse and cell data from one research group. It has never been tested in people. Treat it as an unproven research compound.

References

• Djillani A, Pietri M, Moreno S, Heurteaux C, Mazella J, Borsotto M. Shortened spadin analogs display better TREK-1 inhibition, in vivo stability and antidepressant activity. Front Pharmacol. 2017;8. PMID 28955242.
• Heurteaux C, et al. Deletion of the background potassium channel TREK-1 results in a depression-resistant phenotype. Nat Neurosci. 2006;9:1134-1141. PMID 16906152.
• Pietri M, Djillani A, Mazella J, Borsotto M, Heurteaux C. First evidence of protective effects on stroke recovery and post-stroke depression induced by sortilin-derived peptides. Neuropharmacology. 2019;158:107715. PMID 31325429.
• Daziano G, et al. Sortilin-derived peptides promote pancreatic beta-cell survival through CREB signaling pathway. Pharmacol Res. 2021;167. PMID 33737242.
• Mazella J, et al. Spadin, a sortilin-derived peptide targeting rodent TREK-1 channels: a new concept in the antidepressant drug design. PLoS Biol. 2010. PMID 20405001.