PE-22-28
TREK-1 Channel Blocker | Shortened Spadin Analog
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.
Mechanism of Action
Selectively blocks TREK-1 potassium channels (IC50: 0.12 nM). Enhances serotonin neurotransmission in dorsal raphe nucleus, triggering CREB activation and hippocampal neurogenesis.
Key Benefits
- Rapid antidepressant effects within 4 days (preclinical)
- Hippocampal neurogenesis and synaptogenesis
- Enhanced serotonergic neurotransmission
- Extended ~23 hour duration of action
- 300-500x greater potency than full-length Spadin
GVSWGL?Glycine
Position 1
Valine
Position 2
Serine
Position 3
Tryptophan
Position 4
Glycine
Position 5
Leucine
Position 6
Arg (GVSWGLR)
Position 7
Mental Health
- Depression
Primary research focus with rapid effects in behavioral models within 4 days.
- Anxiety
Anxiolytic properties demonstrated in preclinical anxiety models.
Neurogenesis
- Hippocampal Neurogenesis
Nearly doubles BrdU-positive cells after 4-day treatment.
- Synaptogenesis
Promotes new synapse formation through CREB activation.
Cognition
- Memory Support
Hippocampal and prefrontal cortex TREK-1 expression supports memory.
- Neuroprotection
Potential ischemic protection and neuronal survival support.
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
Both enhance serotonergic pathways; monitor for excessive activity.
Complementary neurogenesis and cognitive support.
Different mechanisms for anxiety and mood support.
Complementary neuroplasticity pathways.
Different mechanisms, no contraindications.
Serotonin syndrome risk.
Measurable antidepressant effects in preclinical models
Neurogenesis and synaptogenesis processes established
Potential mood and cognitive improvements emerge
Sustained treatment allows full neurogenic effects
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
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
- 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.
Disclaimer
This information is for educational and research purposes only. Consult a healthcare professional before use.