PE-22-28
Spadin-derived TREK-1 channel blocker — fast-acting antidepressant effects in animal models, unique non-monoaminergic mechanism.
Research facts
| Half-life | Unknown |
|---|---|
| Route | SubQ / Nasal (experimental) |
| Typical dose | No established human dose |
| Frequency | Unknown |
| Solvent | Bacteriostatic water |
| pH | N/A |
| Stability | Unknown |
Mechanism of action
PE-22-28 is a synthetic analogue of spadin, a peptide derived from the NTSR3/sortilin protein. It acts as a selective blocker of the TREK-1 potassium channel — a two-pore domain potassium channel that is overactive in depression and whose activity is downregulated by conventional antidepressants. TREK-1 blockade promotes neuroplasticity and has demonstrated rapid antidepressant effects in multiple animal models (comparable to classical antidepressants but with faster onset). PE-22-28 is a potency-optimised, metabolically stabilised analogue of spadin with enhanced CNS penetration. It represents a genuinely novel antidepressant mechanism.
Documented effects (research-model)
- Rapid antidepressant effects in animal models
- Novel TREK-1 potassium channel mechanism (non-monoaminergic)
- Potential for faster onset than conventional antidepressants
- Preclinical evidence in multiple depression models
Research protocols
| Protocol | Dose | Frequency | Cycle | Vial |
|---|---|---|---|---|
| Experimental Only | No human dose established | Unknown | Unknown | N/A |
Research context only. Not medical advice. Consult a qualified healthcare professional before any protocol decision.
Synergies
- Selank MODERATE
PE-22-28 (antidepressant via TREK-1) + Selank (anxiolytic via GABA/serotonin). Potential combination for comorbid depression-anxiety.
Myths & misconceptions
Evidence gaps
- No human clinical data.
- TREK-1 has roles beyond neurological function — systemic effects unknown.
- Optimal delivery route for CNS access in humans not characterised.
Safety notes
No human safety data. Very early preclinical stage. Research context only.
Biomarkers to monitor
Primary-source citations
- PMID 27748714 — PE-22-28, a spadin analogue with improved antidepressant activity (Br J Pharmacol. 2017)
Frequently asked
What is PE-22-28?
PE-22-28 (Spadin Analogue — Antidepressant Peptide) is a research compound classified in our library as Tier D — Animal or in-vitro data only.. Spadin-derived TREK-1 channel blocker — fast-acting antidepressant effects in animal models, unique non-monoaminergic mechanism.
What is the evidence tier for PE-22-28?
We classify PE-22-28 as Tier D: Animal or in-vitro data only. See our full peptide evidence tiers explainer for how we assign S/A/B/C/D.
What is the research dose of PE-22-28?
For PE-22-28, typical research dose is No established human dose, route is SubQ / Nasal (experimental), half-life is Unknown. Protocols vary by research goal — see the protocols section on this page for standard and advanced dosing schedules. Research use only, not medical advice.
Is PE-22-28 safe?
No human safety data. Very early preclinical stage. Research context only — no compound on this site is approved for human therapeutic use unless explicitly noted.