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.
Overview
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.
Research indications
What the compound has been studied for, grouped by body system. Effect size is the reported magnitude where it was measured — not a recommendation.
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.
A large effect in a weak study and a small effect in a strong one are different things. Effect size is never evidence of use in people.
- Class
- Linear heptapeptide
- Chain length
- 7 residues
- Molecular weight
- 773.89 Da
- Half-life
- ~23 h
- Typical dose
- 50-200mcg daily
- Frequency
- Once daily
- Cycle length
- 4-8 weeks
- Storage
- Refrigerate at 2-8°C, use within 4-6 weeks
Molecular data
- Type
- Linear heptapeptide
- Molecular weight
- 773.89 Da
- Chain length
- 7 residues
- Half-life
- 1380 min
Dosing reference
Doses reported in the literature and by suppliers. These are a record of what has been used in research — reference, never instruction.
| Context | Route | Amount | Frequency |
|---|---|---|---|
| Antidepressant Effect | SubQ | 50-200mcg | Once daily |
| Neurogenesis Support | SubQ | 100-200mcg | Once daily |
| General Use | Oral | Higher than injectable (specific dose TBD) | Daily |
| General Use | Intranasal | 100-300mcg (estimated) | Daily |
Interactions
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.
Quality checklist
- ✓White to off-white lyophilized powder
- ✓Clear, colorless reconstituted solution
- ✓Certificate of Analysis with >98% purity
- ✓Proper cold-chain shipping
- !Research compound only, not FDA-approved
- !Quality varies by supplier
- ×Cloudy, discolored, or particulate appearance
- ×Clumped or sticky powder indicating moisture damage
What to expect
Safety
- No effects on TREK-2, TRAAK, TASK-1 channels observed
- No cardiac dysfunction or seizures in preclinical studies
- Serotonin syndrome signs
- Severe persistent headaches
- Cardiac symptoms
- Seizure activity
- Severe mood changes or suicidal ideation
- Pregnancy and breastfeeding
- Concurrent MAOI use
FAQ
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.