PE-22-28 (Mini-Spadin)
TREK-1 Channel Blocker | Shortened Spadin Analog
Community Research
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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
GVSWGL?Glycine
Position 1
Valine
Position 2
Serine
Position 3
Tryptophan
Position 4
Glycine
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.
| Goal | Dose | Frequency | Route |
|---|---|---|---|
| Antidepressant Effect | 50-200mcg | Once daily | SubQ |
| Neurogenesis Support | 100-200mcg | Once daily | SubQ |
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
- Shortened Spadin Analogs Display Better TREK-1 Inhibition(2017)
PE-22-28 IC50 0.12 nM vs 40-60 nM for Spadin; ~23 hour duration. Frontiers in Pharmacology.
- Spadin: A Sortilin-Derived Peptide Targeting TREK-1 Channels(2010)
Original discovery of TREK-1 blockade as antidepressant mechanism. PLOS Biology.
- TREK-1 Deletion Results in Depression-Resistant Phenotype(2006)
TREK-1 knockout mice show depression-resistant behavior in 5 tests. Nature Neuroscience.
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Disclaimer
This information is for educational and research purposes only. Consult a healthcare professional before use.