PE-22-28
Also known as: Spadin derivative · GVSWGLR · PE22-28
A synthetic heptapeptide derived from the prosegment of sortilin that acts as a selective TREK-1 potassium channel antagonist. Produces rapid antidepressant effects within 4 days — far faster than SSRIs — and demonstrates neuroprotection in stroke and ischemia models.
What is PE-22-28? A synthetic heptapeptide derived from the prosegment of sortilin that acts as a selective TREK-1 potassium channel antagonist. Produces rapid antidepressant effects within 4 days — far faster than SSRIs — and demonstrates neuroprotection in stroke and ischemia models.
How does PE-22-28 work? PE-22-28 competitively blocks the TREK-1 (TWIK-related potassium channel) two-pore domain K+ channel, which is implicated in depression and neuronal vulnerability. TREK-1 blockade depolarizes neurons and rapidly upregulates BDNF and neurogenesis in the hippocampus. Unlike SSRIs which require 2-4 weeks, antidepressant effects appear within 4 days in rodent models, consistent with direct neuroplasticity enhancement.
Benefits of PE-22-28: Rapid-onset antidepressant effects (4-day onset vs weeks for SSRIs); TREK-1 potassium channel selective antagonist; Promotes hippocampal neurogenesis; Neuroprotection in ischemia and stroke models; Anxiolytic properties without sedation; BDNF upregulation; May complement or potentiate conventional antidepressants
PE-22-28 dosage: Intranasal delivery preferred for CNS effects. 300-600mcg/day studied in preclinical models. No established human dose.
PE-22-28 half-life: Short (estimated 1-2 hours)
Research status: Research Only
Source: PeptideWiki — https://www.peptide-wiki.net/peptides/pe-22-28
Mechanism of Action
PE-22-28 competitively blocks the TREK-1 (TWIK-related potassium channel) two-pore domain K+ channel, which is implicated in depression and neuronal vulnerability. TREK-1 blockade depolarizes neurons and rapidly upregulates BDNF and neurogenesis in the hippocampus. Unlike SSRIs which require 2-4 weeks, antidepressant effects appear within 4 days in rodent models, consistent with direct neuroplasticity enhancement.
Benefits
- Rapid-onset antidepressant effects (4-day onset vs weeks for SSRIs)
- TREK-1 potassium channel selective antagonist
- Promotes hippocampal neurogenesis
- Neuroprotection in ischemia and stroke models
- Anxiolytic properties without sedation
- BDNF upregulation
- May complement or potentiate conventional antidepressants
Side Effects & Risks
- Limited human data — rodent models primarily
- Potential for excessive neuronal excitability at high doses
- Headache
- Currently research use only
Where to Buy PE-22-28
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From
$55.00
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Storage & Reconstitution Guide
Storage Temperature
-20°C (lyophilized)
24 months (lyophilized), 28 days (reconstituted)
Reconstitution Solvent
Bacteriostatic water (BAC water)
Swirl gently — do not shake or vortex
Handling Notes
Protect lyophilized peptide from moisture and light. Once reconstituted, keep refrigerated. Discard if solution becomes cloudy or discolored. Use insulin syringe for precise dosing.
Step-by-Step Reconstitution
Gather supplies
BAC water, insulin syringe, alcohol swabs, vial
Disinfect tops
Swab rubber stoppers of both vials with alcohol
Draw BAC water
Pull desired mL of BAC water into syringe
Inject slowly
Inject BAC water down the side of the peptide vial, swirl gently to dissolve
Preclinical Research & Reviews1
PE-22-28, a spadin analog, displays antidepressant-like effects
PE-22-28 produced rapid antidepressant-like effects within 4 days in mouse models via TREK-1 channel inhibition, with neuroprotection against LPS-induced neuroinflammation.
Onset
4-day antidepressant effect vs 2-4 weeks for SSRIs
Mechanism
TREK-1 potassium channel antagonist
Additional
Neuroprotection against neuroinflammation
Molecular Structure
- CAS Number
- 1801959-12-5
- PubChem CID
- 165437303
- Molecular Weight
- 773.89 Da
- Mol. Formula
- C35H55N11O9
- Amino Acids
- 7-AA peptide
Research Protocol
- Dose Range
- 200–600 mcg
- Frequency
- Once or twice daily intranasal or subcutaneous
- Cycle
- 2-4 weeks on, 1-2 weeks off
- Half-Life
- Short (estimated 1-2 hours)
- Routes
- intranasalsubcutaneous injection
- Notes
- Intranasal delivery preferred for CNS effects. 300-600mcg/day studied in preclinical models. No established human dose.
Legal & Regulatory Status
Sold for research purposes only. Not for human use. Laws vary by country.
Commonly Stacked With
View all peptide stacks →External Resources
PeptideWiki Research Team
Evidence-based research data sourced from PubMed and ClinicalTrials.gov · Last updated: February 25, 2026
Frequently Asked Questions About PE-22-28
What is PE-22-28?▾
A synthetic heptapeptide derived from the prosegment of sortilin that acts as a selective TREK-1 potassium channel antagonist. Produces rapid antidepressant effects within 4 days — far faster than SSRIs — and demonstrates neuroprotection in stroke and ischemia models.
What are the benefits of PE-22-28?▾
Rapid-onset antidepressant effects (4-day onset vs weeks for SSRIs)
What are the benefits of PE-22-28?▾
TREK-1 potassium channel selective antagonist
What are the side effects of PE-22-28?▾
Limited human data — rodent models primarily
What is the recommended dosage for PE-22-28?▾
Intranasal delivery preferred for CNS effects. 300-600mcg/day studied in preclinical models. No established human dose.
How long should a PE-22-28 cycle last?▾
2-4 weeks on, 1-2 weeks off
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