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.
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
1 option across 1 vendor · Sorted cheapest first · All include direct product link
From
$55.00
All links are affiliate links — PeptideWiki earns a commission at no extra cost to you. Coupon codes apply at checkout. Prices and availability may change. Always verify COA before purchasing.
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
More in Cognitive & Nootropic
EDR tetrapeptide
A synthetic tripeptide (Glu-Asp-Arg) from the Khavinson peptide bioregulator series targeting the brain and pineal gland. Reduces neuronal apoptosis, improves cognitive function in aging models, and normalizes circadian rhythm disruption. Distinct from Epithalon despite also targeting the pineal gland.
Cerebral cortex peptide bioregulator
A peptide bioregulator targeting the cerebral cortex and CNS from the Khavinson series. Normalizes cortical neuron function, reduces age-related neurodegeneration, and improves cognitive function. Particularly studied for age-associated cognitive decline, vascular dementia, and post-stroke recovery.
GVS-111
A synthetic dipeptide nootropic approximately 1000x more potent than piracetam. Stimulates BDNF and NGF expression with significant neuroprotective and cognitive-enhancing effects.
FPF-1070
A complex mixture of low-molecular-weight neuropeptides derived from porcine brain proteins. The only peptide-based nootropic with robust clinical evidence for Alzheimer disease and brain injury.