Cognitive
PE-22-28
Longevity
7
Amino acids
Molecular weight
Peptide
Type
PE-22-28 is a synthetic heptapeptide (sequence: Gly-Val-Ser-Trp-Gly-Leu-Arg) derived from spadin, an endogenous fragment of sortilin, engineered to be a more potent and stable TREK-1 potassium channel antagonist. It selectively inhibits the TREK-1 two-pore domain potassium channel with an IC50 of 0.12 nM — over 300-fold more potent than spadin — producing rapid antidepressant-like effects within 4 days and promoting hippocampal neurogenesis in rodent models. Preclinical studies have also demonstrated neuroprotective activity in stroke and neuroinflammation models, and improved in vivo stability that extends effective duration of action to approximately 23 hours per dose.
Top researched benefits
Overview of PE-22-28
PE-22-28 acts as a high-affinity antagonist of TREK-1, a two-pore domain (K2P) potassium channel whose constitutive activity suppresses neuronal excitability and serotonergic signaling. By blocking TREK-1, PE-22-28 increases neuronal firing rates, upregulates BDNF expression, promotes hippocampal neurogenesis, and enhances synaptogenesis as measured by elevated PSD-95 expression in cortical neurons.
mental health
- Primary research focus with rapid effects in behavioral models within 4 days.
- Anxiolytic properties demonstrated in preclinical anxiety models.
neurogenesis
- Nearly doubles BrdU-positive cells after 4-day treatment.
- Promotes new synapse formation through CREB activation.
cognition
- Hippocampal and prefrontal cortex TREK-1 expression supports memory.
- Potential ischemic protection and neuronal survival support.
Typical Dose
400mcg per dose
Frequency
once daily (intranasal)
Cycle Duration
8 weeks standard, up to 16 weeks with optional extension
Storage
Lyophilized: store at -20°C. Reconstituted: refrigerate at 2–8°C, use within 28 days.
Chemical Makeup
Key benefits
Produces rapid-onset antidepressant-like effects in rodent forced-swim models after as few as 4 days of treatment, without sedative or addictive properties
Promotes hippocampal neurogenesis and synaptogenesis, increasing synaptic density markers (PSD-95) in mouse cortical neurons within 4 days
Upregulates BDNF (brain-derived neurotrophic factor) signaling, supporting emotional resilience and long-term neural plasticity
Demonstrated neuroprotective effects in stroke models, reducing motor and cognitive dysfunction and improving post-ischemic recovery while preserving dopaminergic neurons
Community interest
This peptide is still gaining traction in the community.
TREK-1 Antagonist | Antidepressant & Neurogenesis
This overview is informational and based on aggregated descriptions from studies and user reports.
Was it helpful?YesNoPE-22-28 Molecular Information
View the scientifc details of PE-22-28.
7
Amino Acids
PE-22-28
Gly
Gly
Position 1
Val
Val
Position 2
Ser
Ser
Position 3
Trp
Trp
Position 4
Gly
Gly
Position 5
Leu
Leu
Position 6
Arg
Arg
Position 7
Molecular Weight
773.89DaChain Length
7Amino AcidsType
PeptidePE-22-28 Protocols
Subcutaneous injection is the primary route for PE-22-28, offering optimal bioavailability for its TREK-1 channel inhibition and antidepressant effects. Intramuscular injection is a viable alternative with sustained absorption. The abdomen, outer thighs, and upper arms are preferred sites for subcutaneous administration.
| Goal | Dosage | Frequency | Route |
|---|---|---|---|
| Depression / Mood Regulation | 100 | 1 day range | SubQ |
| Titration Start (Weeks 1–2) | 50 | 1 day range | SubQ |
| Standard Maintenance (Weeks 3–8) | 100 | 1 day range | SubQ |
| Escalated Protocol (Weeks 9–12) | 150 | 1 day range | SubQ |
| Cognitive Enhancement / Neuroprotection | 100 | 1 day range | SubQ |
| Post-Stroke Recovery | 150 | 1 day range | SubQ or IM |
Reconstitution Instructions
Materials needed:
Steps to reconstitute
- Allow the PE-22-28 vial (typically 10 mg) to reach room temperature before reconstitution
- Draw 3.0 mL of bacteriostatic water (BAC water) into a sterile syringe
- Inject the BAC water slowly down the inner wall of the vial — never directly onto the lyophilized powder — to prevent foaming and degradation
- Gently swirl or roll the vial between your palms until fully dissolved; do not shake
- The resulting solution will be approximately 3.33 mg/mL (3,330 mcg/mL); label the vial with the date of reconstitution
- Refrigerate the reconstituted vial at 2–8°C, protected from light; use within 28 days
- For injection, draw the target dose volume into an insulin syringe and remove any air bubbles
- Pinch a 1–2 inch skin fold at the chosen injection site and insert the needle at a 45–90° angle
- Inject the solution slowly and steadily over 3–10 seconds; hold the needle in place for 5–10 seconds post-injection before withdrawing
- Rotate injection sites systematically — abdomen (at least 2 inches from navel), outer thighs, upper arms — to prevent lipohypertrophy
PE-22-28 Cycle
The PE-22-28 Cycle section explains how long a typical cycle lasts and what to expect during each phase. Over time, your body can become less responsive with continuous use.
Taking breaks between cycles may help maintain effectiveness and support better overall results.
- Day 1-4
- Measurable antidepressant effects in preclinical models
- Week 1-2
- Neurogenesis and synaptogenesis processes established
- Week 2-4
- Potential mood and cognitive improvements emerge
- Week 4-8
- Sustained treatment allows full neurogenic effects
Dosing tools
PE-22-28 Peptide Dosage Calculator
Calculate peptide doses with our visual syringe guide.
mg
Enter the total amount of peptide in the vial in milligrams (as stated on the label).
The dose you want to inject per administration, in mcg or mg.
1,000 mcg = 1 mg
1 mL
2 mL
3 mL
5 mL
Custom
Volume of bacteriostatic water you add to reconstitute the powder. Use BAC water for preservation.
Injection Results
Based on your vial and dilution inputs.
PE-22-28
SINGLE COMPOUNDVolume per injection
0.05
mL
Concentration
10.00
mg/mL
Doses per vial
20
doses
Total injections per vial
20 injections
How it works
Based on a 10 mg PE-22-28 vial diluted with 1 mL of bacteriostatic water, each 500 mcg injection equals 0.05 mL.
1mL / 100 units
5 units
0.050 mL
Reference Guide
Dosing Cycle
- Peptide
- PE-22-28
- Dosing
- 400mcg per dose
- Dosing Frequency
- once daily (intranasal)
- Cycle Duration
- 8 weeks standard, up to 16 weeks with optional extension
- Storage
- Lyophilized: store at -20°C. Reconstituted: refrigerate at 2–8°C, use within 28 days.
Note: Triple agonist; microdose for fewer side effects
Reconstitution Tips
- Use bacteriostatic water (BAC) — contains 0.9% benzyl alcohol for preservation
- Inject water slowly — aim down the vial wall, not directly onto powder
- Never shake — gently swirl or roll the vial until dissolved
- Store properly — refrigerate at 2-8°C after reconstitution
- Use within 28 days — most reconstituted peptides remain stable for about 4 weeks
- Keep sterile — always clean vial tops with alcohol before drawing
Peptide Interactions
Research suggestions of PE-22-28 interactions with other common peptides and substances.
Side effects
Contraindications
Pregnancy and breastfeeding
Concurrent MAOI use
Stop signs
Serotonin syndrome signs
Severe persistent headaches
Cardiac symptoms
Seizure activity
Severe mood changes or suicidal ideation
Bad signs
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Frequently asked questions
What is a peptide dosage calculator?
A peptide dosage calculator is a free tool that converts your vial size, bacteriostatic water volume, and target dose into an exact syringe draw volume. Instead of doing the reconstitution math by hand, you enter three inputs and instantly get the concentration of your solution and how many milliliters or syringeunits to draw. This calculator works for single peptide compounds and multi-peptide blends.
How do I calculate peptide dosage from a vial?
To calculate your peptide dose, divide the total peptide content of your vial in micrograms by the volume of bacteriostatic water you added in milliliters. This gives you your solution concentration in mcg/mL. Then divide your target dose by that concentration to get your draw volume. For example, a 5mg (5,000 mcg) vial reconstituted with 2mL of BAC water gives a concentration of 2,500 mcg/mL. A 250 mcg dose would require drawing 0.1mL. This calculator automates all of those steps instantly.
How much Bacteriostatic water should I add to a peptide vial?
Most people add 2mL to 3mL of bacteriostatic water per vial, but the right amount depends on the dose you want to draw and the syringe size you are using. Adding 1mL to a 5mg vial gives you a concentration of 5,000 mcg/mL, making each dose very small in volume. Adding 2mL gives you 2,500 mcg/mL, which is easier to measure on a standard insulin syringe. A general guideline is to choose a volume that puts your typical dose somewhere between 10 and 30 units on a U-100 syringe. Use the calculator above to test different water volumes and find what works for your dose.
How are peptides different from proteins?
Both are made of amino acids, but peptides are much smaller than proteins. Because of their tiny size, peptides can act like tiny messengers in the body, sending specific signals to your cells to tell them exactly what to do.
PE-22-28Research References
PE-22-28 is a preclinical compound
PE-22-28
PE-22-28 is a preclinical compound
Shortened Spadin Analogs Display Better TREK-1 Inhibition
PE-22-28 IC50 0.12 nM vs 40-60 nM for Spadin; ~23 hour duration. Frontiers in Pharmacology.
2017
Spadin: A Sortilin-Derived Peptide Targeting TREK-1 Channels
Original discovery of TREK-1 blockade as antidepressant mechanism. PLOS Biology.
2010
TREK-1 Deletion Results in Depression-Resistant Phenotype
TREK-1 knockout mice show depression-resistant behavior in 5 tests. Nature Neuroscience.
2006
Calculate peptide dosages
Learning how to calculate a peptide dose? Use our beginner-friendly peptide dosage, blend, and accumulation calculators. Enter vial size, reconstitution volume, and target dose to get exact draw volumes instantly. No guesswork, just clear guidance that helps prevent common mistakes.
