PE-22-28
Also called Spadin analogue
An experimental seven-amino-acid peptide that blocks the TREK-1 potassium channel, studied as a new approach to depression research. Its findings come from lab and mouse tests, not human trials.
Overview
What it is
A shortened version of spadin, a peptide derived from the sortilin protein. The "22-28" refers to a position in the sequence, not a dose.
How it works
TREK-1 is a potassium channel that affects how nerve cells fire. Blocking it is a different approach from common antidepressants that affect serotonin. Later research suggests spadin's effect on TREK-1 depends on conditions, so the mechanism is not fully settled.
What the research shows
A 2017 study found PE-22-28 strongly inhibited TREK-1 in the lab, produced antidepressant-like behavior in mice, and affected nerve-cell growth markers, with longer-lasting activity than spadin. No human trials were identified.
Studied for
- TREK-1 channel blockinglab
- Antidepressant-like behaviormice
Safety and regulatory status
Safety and side effects
Human side effects and drug interactions are not characterized. A different mechanism does not rule out interactions with antidepressants or mood stabilizers.
Regulatory status
Not approved by the FDA for any use.
Mixing and dosing reference
Reference information only. Read before using this section.
PE-22-28 (10 mg Vial) Dosage Protocol
- Vial
- 10 mg PE-22-28
- Add diluent
- 3 mL
- Concentration
- 3.33 mg/mL
- 1 unit (U-100)
- 33.33 mcg in 0.01 mL
- Route
- Subcutaneous
- How often
- Once per day (subcutaneous).
- Typical range
- 50–200 µg once daily (gradual titration over 8–16 weeks).
- Cycle length
- 12–16 weeks; 8 weeks minimum.
Standard / Gradual Approach
| Week | Daily Dose (µg) | Units (per injection) (mL) |
|---|---|---|
| Weeks 1–2 | 50 µg | 1.5 units (0.015 mL) |
| Weeks 3–4 | 100 µg | 3 units (0.03 mL) |
| Weeks 5–8 | 100 µg | 3 units (0.03 mL) |
| Weeks 9–12 (Optional) | 150 µg | 4.5 units (0.045 mL) |
| Weeks 13–16 (Optional) | 200 µg | 6 units (0.06 mL) |
How to mix
- Draw 3.0 mL bacteriostatic water with a sterile syringe.
- Inject slowly down the vial wall; avoid foaming.
- Gently swirl/roll until dissolved (do not shake).
- Label and refrigerate at 2–8 °C (35.6–46.4 °F), protected from light.
Dosing details
- Start: 50 µg daily for Weeks 1–2 to assess tolerance.
- Increase: 100 µg daily for Weeks 3–8 (standard maintenance dose).
- Optional Titration: 150 µg (Weeks 9–12) or 200 µg (Weeks 13–16) only if well-tolerated and additional effect desired.
- Frequency: Once per day (subcutaneous).
- Cycle Length: 12–16 weeks; 8 weeks minimum.
- Timing: Consistent daily time; rotate injection sites systematically.
Storage
- Lyophilized: Store at −20 °C (−4 °F) in dry, dark conditions; minimize moisture exposure.
- Reconstituted: Refrigerate at 2–8 °C (35.6–46.4 °F); follow product-specific use-by and sterile-handling instructions.
- Allow vials to reach room temperature before opening to reduce condensation; protect from light.
- Bacteriostatic water does not guarantee that a prepared peptide vial remains sterile for a set period. Follow applicable multi-dose vial handling rules; they do not establish this peptide’s chemical shelf life.
Administration technique
- Clean the vial stopper and injection site with alcohol; allow both to air-dry completely.
- Pinch a skinfold of subcutaneous tissue; insert the needle at 45° (or 90° if using very short needles with ample subcutaneous fat).
- Do not aspirate for subcutaneous injections; inject solution slowly and steadily.
- Rotate sites systematically (abdomen at least 2 inches from navel, front/outer thighs, outer upper arms) to prevent lipohypertrophy and maintain absorption consistency.
- Given the very small injection volumes (often ≤0.10 mL), technique precision is critical. Consider using 30- or 50-unit insulin syringes for doses under 10 units to improve measurement accuracy.
- Withdraw needle at the same angle inserted; apply gentle pressure if needed; dispose of syringe immediately in sharps container.
Important notes
- Use new sterile insulin syringes for each injection; dispose in a sharps container immediately.
- Rotate injection sites (abdomen, thighs, upper arms) systematically to reduce local irritation.
- Inject slowly; wait a few seconds before withdrawing the needle to prevent leakage.
- Document daily dose, site rotation, and any observations to maintain protocol consistency.
- Given PE-22-28’s high potency (IC50 ~0.12 nM), conservative dosing is recommended; most preclinical effects occurred at low microgram ranges.
Protocol source: PeptideDosages.com
Common questions
Is PE-22-28 the same as spadin?
No. It is a shorter related peptide; evidence should be matched to the exact compound.
Does it work within days?
That has not been shown in people.
Is it a nootropic?
The research does not establish memory or focus benefits in people.
Found in these blends
Related in Brain and Cognitive Health
Sources and further reading (5)
- Djillani A, et al. Shortened spadin analogs display better TREK-1 inhibition and antidepressant activity. Front Pharmacol, 2017.
- Mazella J, et al. Spadin, a sortilin-derived peptide targeting TREK-1. PLoS Biol, 2010.
- Ma R, Lewis A. Spadin selectively antagonizes arachidonic acid activation of TREK-1. Front Pharmacol, 2020.
- NIMH. Depression.
- Source summary: PeptideDosages.com research overview (rewritten for NVO).