Educational guide
PE-22-28 Overview, Dosing & Safety | Peptide Database
PE-22-28 (Mini-Spadin) TREK-1 Channel Blocker | Shortened Spadin Analog Community Research Join others researching PE-22-28 — share findings, ask questions, and learn from real experiences Synthetic heptapeptide derived from Spadin positions 22-28, functioning
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PE-22-28 (Mini-Spadin)
TREK-1 Channel Blocker | Shortened Spadin Analog
Community Research
Join others researching PE-22-28 — share findings, ask questions, and learn from real experiences
Synthetic heptapeptide derived from Spadin positions 22-28, functioning as potent TREK-1 antagonist with enhanced selectivity and duration versus parent compound. Primary research focus on rapid antidepressant effects.
Selectively blocks TREK-1 potassium channels (IC50: 0.12 nM). Enhances serotonin neurotransmission in dorsal raphe nucleus, triggering CREB activation and hippocampal neurogenesis.
Molecular Data
Glycine
Position 1
Valine
Position 2
Serine
Position 3
Tryptophan
Position 4
Position 5
Leucine
Position 6
Arg (GVSWGLR)
Position 7
Research Indications
Primary research focus with rapid effects in behavioral models within 4 days.
Anxiolytic properties demonstrated in preclinical anxiety models.
Nearly doubles BrdU-positive cells after 4-day treatment.
Promotes new synapse formation through CREB activation.
Hippocampal and prefrontal cortex TREK-1 expression supports memory.
Potential ischemic protection and neuronal survival support.
Dosing Protocols
Subcutaneous injection to abdominal fat or thigh with site rotation.
Antidepressant Effect
50-200mcg
Once daily
SubQ
Neurogenesis Support
100-200mcg
Reconstitution Instructions
PE-22-28 lyophilized powder
Bacteriostatic water
Insulin syringes
Alcohol swabs
1 Inject BAC water slowly down vial wall
2 Gently swirl (do not shake)
3 Store refrigerated 2-8°C
4 Use within 4-6 weeks
Interactions
What to Expect
Side Effects & Safety
Common Side Effects
No effects on TREK-2, TRAAK, TASK-1 channels observed
No cardiac dysfunction or seizures in preclinical studies
Stop Signs - Discontinue if:
Serotonin syndrome signs
Severe persistent headaches
Cardiac symptoms
Seizure activity
Severe mood changes or suicidal ideation
Contraindications
Pregnancy and breastfeeding
Concurrent MAOI use
Quality Checklist
Good Signs
White to off-white lyophilized powder
Clear, colorless reconstituted solution
Certificate of Analysis with >98% purity
Proper cold-chain shipping
Warning Signs
Research compound only, not FDA-approved
Quality varies by supplier
Bad Signs
Cloudy, discolored, or particulate appearance
Clumped or sticky powder indicating moisture damage
Frequently Asked Questions
How much more potent is PE-22-28 compared to full-length Spadin?
PE-22-28 is dramatically more potent—roughly 300-500x more potent than full-length Spadin. This extraordinary difference comes from being a shortened fragment that better mimics the active site. The result is an IC50 of just 0.12 nM for TREK-1 inhibition versus 40-60 nM for Spadin.
Can PE-22-28 work as a standalone antidepressant, or is it just for research?
PE-22-28 shows rapid antidepressant effects in animal models (within 4 days), but it's currently research-only with no human clinical trials completed. It's not approved for therapeutic use. However, the preclinical evidence is strong enough that clinical development may follow if pharmaceutical companies invest in it.
How long does PE-22-28's effect on neurogenesis last?
In preclinical studies, neurogenesis and synaptogenesis establishment begins within 1-2 weeks of treatment. However, we don't know how long effects persist after discontinuation—that depends on sustained CREB activation and whether new neurons survive. Duration data doesn't exist for human use.
Is PE-22-28 safe to combine with SSRIs?
Caution is advised. Both PE-22-28 and SSRIs enhance serotonin. While the interactions section says to 'monitor,' combining them theoretically increases serotonin syndrome risk. Start carefully with your healthcare provider's supervision if considering this combination. Never combine with MAOIs.
References
PE-22-28 IC50 0.12 nM vs 40-60 nM for Spadin; ~23 hour duration. Frontiers in Pharmacology.
Original discovery of TREK-1 blockade as antidepressant mechanism. PLOS Biology.
TREK-1 knockout mice show depression-resistant behavior in 5 tests. Nature Neuroscience.
Related Peptides
Different mechanisms for anxiety and mood support.
Complementary neuroplasticity pathways.
Different mechanisms, no contraindications.
Disclaimer
This information is for educational and research purposes only. Consult a healthcare professional before use.