PE-22-28

Overview

PE-22-28 is a seven-amino-acid peptide cut down from spadin, a natural peptide that French researchers found has fast antidepressant-like effects in mice. It works by blocking a potassium channel in brain cells called TREK-1. All research so far is in cells and mice; it has never been tested in people.

How it works

Proposed from cell and mouse studies. TREK-1 is a potassium 'leak' channel; mice lacking it resist depression-like behavior, which made it a drug target ¹. Spadin, a fragment released from the protein sortilin, blocks TREK-1 ¹. PE-22-28 blocked human TREK-1 far more potently than spadin in cell recordings (IC50 about 0.12 nM vs 40-60 nM), did not affect related channels (TREK-2, TRAAK, TRESK, TASK-1) or the heart-rhythm channel hERG in the lab, and produced antidepressant-like effects and new nerve-cell growth (neurogenesis) in mice after only four days ². Not established in humans.

What research shows

• Mazella et al. 2010, PLoS Biol (cell and mouse study): spadin blocked TREK-1, increased serotonin-neuron firing and reduced depression-like behavior in five mouse tests; a 4-day IV course boosted hippocampal neurogenesis ¹.
• Djillani et al. 2017, Front Pharmacol (cell and mouse study): PE 22-28 inhibited TREK-1 with an IC50 of 0.12 nM; its action lasted up to 23 hours versus about 7 hours for spadin ².
• Same study: in mice, PE 22-28 and analogs reduced immobility in the forced swim test, shortened feeding latency in the novelty-suppressed feeding test after 4 days, and increased neurogenesis and synapse-protein markers ².
• No published human studies were found.

Doses studied in people

No published human dosing data exist; mouse studies used microgram-per-kilogram injections, and doses circulating online are extrapolated from those.

Read this first: these are the amounts given to participants in published studies or written on official prescribing labels, reported for reference. They are not recommendations. Trial doses were chosen for specific patients under medical supervision, and a dose that is safe in one person can be harmful in another.

Weekly protocol

How the schedule looks week by week. Each chart says where it comes from: a prescribing label, a clinical trial, or a protocol commonly reported online.

Reference only, not a recommendation. Charts marked "commonly reported" describe what public sources say people use. They have not been tested in trials, and their safety and effect are unknown. Label and trial schedules were set for specific patients under medical supervision. Use the calculator only to understand the arithmetic.

Vial math

Many research vials hold 5 or 10 mg of powder. This table shows how much ends up in each mark on a U-100 insulin syringe for common amounts of added liquid. It is arithmetic only, not a dose.

More sizes: all vial sizes · How this works: Syringes and units · Reconstitution guide.

Safety

• No human safety data; short- and long-term risks are unknown.
• In lab tests, PE 22-28 analogs did not affect the hERG heart channel, and earlier work on spadin reported no harmful effects on pain, ischemia or the heart in animals ²; these do not establish human safety.
• TREK-1 is also involved in pain sensing and in protecting nerve cells during stroke and seizures in animal models ², so blocking it could in theory have unwanted effects.
• Unregulated 'research' products may vary in purity and identity.

Report side effects of any drug or product to the FDA through MedWatch. For a possible poisoning in the US, call Poison Control at 1-800-222-1222.

Legal status

FDA

Not FDA-approved; no human trials.

Compounding

Not named on FDA's 503A Category 2 page or withdrawn-nominations table (current as of 04/22/2026), and not found on FDA's 503A nominations list as retrieved ³⁴.

Sports (WADA)

Not named on the 2026 Prohibited List. As a substance with no government approval for human use, it would likely fall under S0 (non-approved substances, prohibited at all times); athletes should confirm with their anti-doping organization ⁵.

Other

No approval in any country found.

Rules change often. See Legal status of peptides for how these categories work.

History

Researchers at the Institut de Pharmacologie Moléculaire et Cellulaire (CNRS, Sophia Antipolis, France), led by Jean Mazella, Catherine Heurteaux and Marc Borsotto, described spadin in PLoS Biology in 2010 ¹. Because spadin only lasted a few hours in the body, the same group made shorter versions and in 2017 reported that PE 22-28 and two modified forms were more potent and longer-acting in mice ².

Common questions

Related compounds

Sources

1. Mazella J, Pétrault O, Lucas G, et al. Spadin, a Sortilin-Derived Peptide, Targeting Rodent TREK-1 Channels: A New Concept in the Antidepressant Drug Design. PLoS Biol 2010;8(4):e1000355. doi:10.1371/journal.pbio.1000355 Journal
2. 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;8:643. doi:10.3389/fphar.2017.00643 Journal
3. FDA: Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks (content current as of 04/22/2026) Regulatory
4. FDA: Bulk Drug Substances Nominated for Use in Compounding Under Section 503A (category lists) Regulatory
5. WADA 2026 Prohibited List (official English text, Dutch Treaty Series Trb. 2026, 25) Regulatory