Overview
PE-22-28 is a synthetic heptapeptide derived from the sortilin propeptide, functioning as a potent antagonist of TREK-1 potassium channels. The peptide shows preclinical promise for antidepressant effects, neurogenesis enhancement, and neuroprotection without cardiac or metabolic side effects.
Quick Start
– Reconstitution: Add 3.0 mL bacteriostatic water to achieve ~3.33 mg/mL concentration
– Standard dosing range: 50–200 µg once daily via subcutaneous injection
– Measurement convenience: At the recommended concentration, 1 insulin unit ≈ 33.3 µg
– Duration: 12–16 weeks minimum (8 weeks baseline)
– Storage (lyophilized): −20 °C; after reconstitution: 2–8 °C for up to 4 weeks
Dosing Schedule
Standard Gradual Titration (3 mL reconstitution)
| Period | Daily Dose | Insulin Units | Volume (mL) |
|---|---|---|---|
| Weeks 1–2 | 50 µg | 1.5 | 0.015 |
| Weeks 3–8 | 100 µg | 3 | 0.03 |
| Weeks 9–12 (optional) | 150 µg | 4.5 | 0.045 |
| Weeks 13–16 (optional) | 200 µg | 6 | 0.06 |
Frequency: Once daily via subcutaneous injection with consistent timing and systematic site rotation.
Reconstitution Instructions
1. Draw 3.0 mL sterile bacteriostatic water using a clean syringe
2. Inject slowly down the vial wall to minimize foaming
3. Gently swirl or roll until fully dissolved (do not shake vigorously)
4. Label the vial with reconstitution date
5. Refrigerate at 2–8 °C in darkness; replace every 4 weeks
Mechanism of Action
PE-22-28 blocks TREK-1 (KCNK2) potassium channels, depolarizing neurons and enhancing excitability. This mechanism increases serotonergic neuron firing and monoamine neurotransmission. According to preclinical research, the peptide produces behavioral improvements within 4 days, significantly increasing markers of hippocampal neurogenesis and dendritic plasticity—effects that typically require weeks with conventional antidepressants.
The molecule represents an optimized analog with superior potency (IC50 ~0.12 nM) and extended duration (~23 hours) compared to its parent compound spadin.
Reported Benefits
– Rapid mood support: Behavioral improvements observed within 4 days in animal models
– Enhanced neuroplasticity: Increased neurogenesis, synaptogenesis markers, dendritic spine density, and BDNF expression
– Neuroprotection: Preserves dopaminergic neurons in stroke models; reduces motor deficits and post-stroke depressive behaviors
– Favorable safety profile: No effects on cardiac channels (hERG), heart rate, blood pressure, glucose, or pain perception in preclinical studies
Important Safety Considerations
– No human data: All evidence derives from cell culture and animal studies; human safety and pharmacokinetics remain unestablished
– Preclinical only: Not FDA-approved for human use
– Potential reactions: Minor injection-site reactions (redness, tenderness) may occur
– Selectivity: Demonstrated high selectivity with no TREK-1-related withdrawal effects observed in preclinical work
Supplies Needed (8–16 week protocol)
PE-22-28 Vials:
– 8 weeks: ~2 vials
– 12 weeks: ~3 vials
– 16 weeks: ~4 vials
Insulin Syringes (U-100):
– 8 weeks: ~56 syringes (7 per week)
– 12 weeks: ~84 syringes
– 16 weeks: ~112 syringes
Bacteriostatic Water (10 mL bottles):
– 8 weeks: 1 bottle
– 12 weeks: 1 bottle
– 16 weeks: 2 bottles
Alcohol Swabs:
– 8 weeks: ~2 boxes (100-count)
– 12 weeks: ~2 boxes
– 16 weeks: ~3 boxes
Injection Technique
– Clean vial stopper and injection site with alcohol; allow complete air-drying
– Pinch subcutaneous tissue; insert needle at 45° angle (90° for ample subcutaneous fat)
– Do not aspirate for subcutaneous injections
– Inject solution slowly and steadily
– Rotate injection sites systematically: abdomen (2+ inches from navel), thighs, upper arms
– For doses under 10 units, consider 30- or 50-unit syringes for improved accuracy
– Dispose of syringes immediately in sharps container
Storage Instructions
Lyophilized form: Store at −20 °C in dry, dark conditions with minimal moisture exposure
Reconstituted form: Refrigerate at 2–8 °C; use within 4 weeks for optimal potency
Allow vials to reach room temperature before opening to reduce condensation. Replace vials every 4 weeks; bacteriostatic water sterility is guaranteed only 28 days after first puncture.
Lifestyle Complementary Strategies
– Maintain consistent sleep (7–9 hours nightly) to support neurogenesis
– Engage in regular aerobic and resistance training to enhance BDNF and mood pathways
– Follow nutrient-dense diet rich in omega-3 fatty acids, antioxidants, and B-vitamins
– Practice stress management: meditation, mindfulness, therapy
– Incorporate cognitive training and novel learning activities to leverage enhanced plasticity
Documentation Recommendations
Maintain a daily log including:
– Injection dose and time
– Injection site location
– Any observations or reactions
– Overall wellness notes
Important Notes
– Use fresh sterile syringes for each injection
– Given PE-22-28’s high potency, conservative dosing is recommended; most preclinical effects occurred at low microgram ranges
– This protocol is for therapeutic educational purposes only and does not constitute medical advice, diagnosis, or treatment
– Consult qualified healthcare professionals before considering experimental compounds
—
Disclaimer: This content is intended for research and educational purposes only. PE-22-28 is a research peptide not approved for human use. All information derives from preclinical studies; no human clinical trials have been published.