PE-22-28
Also known as: PE-22-28 Peptide, Spadin analog, Neurogenic Antidepressant Peptide
PE-22-28 is a synthetic analog of spadin derived from sortilin, designed to block TREK-1 potassium channels with rapid-onset antidepressant and neurogenic effects. It shows fast-acting depression relief (within 24 hours) and promotes hippocampal neurogenesis.
Half-Life
Relatively short; CNS effects may persist due to neurogenic mechanisms
Route
SubQ, Intranasal
Category
Cognitive Enhancement
Studies
1 reference
Key Benefits
- Rapid-onset antidepressant effects (within 24 hours)
- Promotes hippocampal neurogenesis
- Improves cognitive performance and memory
- Reduces anxiety and depressive behavior
- Novel mechanism — does not act on serotonin/dopamine/GABA receptors directly
- May help treatment-resistant depression
- Neuroprotective effects
Mechanism of Action
TREK-1 (TWIK-related K⁺ channel 1) is a two-pore domain potassium channel expressed in serotonergic raphe neurons. TREK-1 hyperpolarizes these neurons, suppressing serotonin release. PE-22-28, like its parent compound spadin, blocks TREK-1 channels to depolarize serotonergic neurons and increase serotonin release. Additionally, PE-22-28 activates BDNF-TrkB signaling in the hippocampus, promoting adult neurogenesis (new neuron formation) — a mechanism thought to underlie the sustained antidepressant effect distinct from fast serotonergic effects.
Dosing Protocols
Antidepressant / Neurogenic Protocol
- Dose
- 200–400 mcg
- Frequency
- Once daily
- Timing
- Morning SC injection or intranasal
- Cycle
- 4–12 weeks
Neurogenic effects may require 2–4 weeks to manifest fully; fast serotonergic effects may be felt sooner
Cognitive Enhancement
- Dose
- 100–200 mcg
- Frequency
- Daily or 5x per week
- Timing
- Morning
- Cycle
- 4–8 weeks
Cycle: 8 weeks on, 4 weeks off
Calculate your draw volume
Enter your vial size and BAC water to get exact injection volumes
Side Effects
- Generally well tolerated in animal models
- Limited human data available
- Possible mild headache or transient mood changes at initiation
- Injection site reactions (SC)
Contraindications
Limited clinical human safety data. Use with caution alongside other serotonergic medications. Not for use in bipolar disorder without psychiatric supervision.
Storage
Lyophilized: -20°C. Reconstituted: 4°C, use within 30 days. Protect from light.
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Clinical Research
- 1.Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity
Djillani A, Pietri M, Moreno S, Heurteaux C, Mazella J, Borsotto M · Frontiers in pharmacology · 2017PubMed Verified
Medical disclaimer: This information is for educational purposes only and does not constitute medical advice. Many compounds listed are research chemicals not approved for human use. Always consult a qualified healthcare professional before starting any protocol.
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