PE-22-28 dosage and protocol
PE-22-28 is a synthetic heptapeptide (GVSWGLR) derived from the sortilin propeptide, engineered as a potent and selective TREK-1 potassium channel antagonist. Preclinical studies show rapid antidepressant-like effects within 4 days, enhanced hippocampal neurogenesis and synaptogenesis, neuroprotection in stroke models, and a favorable safety profile with no cardiac or metabolic side effects. Represents a shortened, optimized analog of spadin with superior potency (IC50 ~0.12 nM vs 40–60 nM for spadin).
- Vial size: 10 mg
- Reconstitution: 3 mL bacteriostatic water
- Concentration: 3.33 mg/mL
- Administration: subcutaneous
Research areas
- Antidepressant
- Neuroplasticity
- Neuroprotection
- Mood Enhancement
- Cognitive Function
- Neurogenesis
Quick start
- Reconstitute: Add 3.0 mL bacteriostatic water to the 10 mg vial for about 3.33 mg/mL
- Typical dose: 50 mcg daily, increasing to 100 mcg daily; optional 150-200 mcg in extended phases
- Easy measuring: At 3.33 mg/mL, 1 unit = 0.01 mL = 33.3 mcg on a U-100 syringe; 50 mcg is 1.5 units and 100 mcg is 3 units
- Storage: Lyophilized at -20°C; refrigerate at 2-8°C after mixing and replace the vial every 4 weeks
Dosing protocol
| Phase | Dose | Frequency | Volume |
|---|---|---|---|
| Weeks 1–2 | 50mcg | Once daily | 0.015mL |
| Weeks 3–8 | 100mcg | Once daily | 0.03mL |
| Weeks 9–12 (Optional) | 150mcg | Once daily | 0.045mL |
| Weeks 13–16 (Optional) | 200mcg | Once daily | 0.06mL |
How it works
PE-22-28 is a seven-amino-acid peptide (GVSWGLR) derived from spadin, which itself comes from the propeptide released when the sortilin receptor matures. Like spadin, it blocks TREK-1, a two-pore-domain potassium channel expressed in brain regions involved in mood. Mice lacking TREK-1 are resistant to depression-like behaviour, and blocking the channel increases neuronal excitability and serotonergic signalling, which is thought to underlie the antidepressant-like effect. In rodent studies, PE-22-28 and related shortened spadin analogues produced antidepressant-like effects in behavioural tests within about four days, compared with the several weeks typical of SSRIs in comparable models. Treated mice also showed increased hippocampal neurogenesis and synaptic protein markers, and spadin analogues have shown neuroprotective effects in rodent stroke models. Laboratory work reported much higher potency at TREK-1 than spadin and longer persistence in the body. Published animal studies did not report the cardiac or seizure-related problems that might be expected from blocking a potassium channel, but these were limited in scope. There are no published human clinical trials, so its effects on mood, safety and dosing in people are unknown.
Reconstitution steps
- Draw 3.0mL 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, protected from light
Storage
Store lyophilized at −20°C (−4°F) in dry, dark conditions. After reconstitution, refrigerate at 2–8°C; use within 4 weeks. Replace vial every 4 weeks even if peptide remains.
Important notes
- Research use only
- High potency (IC50 ~0.12 nM) — conservative low-dose approach is essential
- Most preclinical effects occurred at low microgram ranges; most researchers find 100–150mcg/day sufficient
- Rapid antidepressant-like effects observed within 4 days in preclinical models
- Highly selective — no effects on hERG channels, heart rate, blood pressure, or glucose in preclinical studies
- Replace reconstituted vial every 4 weeks; rotate injection sites systematically
- Note: PE-22-28 is distinct from PE-22-88; ensure correct compound identity before use
Supplies
- Bacteriostatic water
- Insulin syringes (U-100, 30- or 50-unit recommended)
- Alcohol swabs