PE-22-28
Also known as: Mini-Spadin
TREK-1 Channel Blocker | Shortened Spadin Analog
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.
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
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.
Molecular data
- Type
- Linear heptapeptide
- Half-life
- Approximately 23 hours
Sequence
Gly-Val-Ser-Trp-Gly-Leu-Arg (GVSWGLR)
Indications
What the research community uses this compound for, with self-reported effectiveness.
Mental Health
Depression
Most effectivePrimary research focus with rapid effects in behavioral models within 4 days.
Anxiety
ModerateAnxiolytic properties demonstrated in preclinical anxiety models.
Neurogenesis
Hippocampal Neurogenesis
Most effectiveNearly doubles BrdU-positive cells after 4-day treatment.
Synaptogenesis
EffectivePromotes new synapse formation through CREB activation.
Cognition
Memory Support
EffectiveHippocampal and prefrontal cortex TREK-1 expression supports memory.
Neuroprotection
ModeratePotential ischemic protection and neuronal survival support.
Dosing protocols
Common protocols by delivery method. Adjust the curve below to model accumulation in your own cycle.
Injectable
Subcutaneous injection to abdominal fat or thigh with site rotation.
| Protocol | Dose | Frequency | Route / duration |
|---|---|---|---|
| Antidepressant Effect | 50-200mcg | Once daily | SubQ |
| Neurogenesis Support | 100-200mcg | Once daily | SubQ |
Preparation
You will need
- PE-22-28 lyophilized powder
- Bacteriostatic water
- Insulin syringes
- Alcohol swabs
Steps
- Inject BAC water slowly down vial wall
- Gently swirl (do not shake)
- Store refrigerated 2-8°C
- Use within 4-6 weeks
Work out the water volume and syringe units in the reconstitution calculator →
Oral
Limited data from animal studies only; higher doses required than injection.
| Protocol | Dose | Frequency | Route / duration |
|---|---|---|---|
| General Use | Higher than injectable (specific dose TBD) | Daily | Oral |
Nasal
Theoretical route; unstudied for PE-22-28 specifically.
| Protocol | Dose | Frequency | Route / duration |
|---|---|---|---|
| General Use | 100-300mcg (estimated) | Daily | Intranasal |
Interactions
Pairwise interactions with other compounds you might be cycling — the same data behind the cycle builder's safety check.
MAOIs
AvoidSerotonin syndrome risk.
SSRIs (Fluoxetine, Sertraline)
MonitorBoth enhance serotonergic pathways; monitor for excessive activity.
Semax/NA-Semax
SynergisticComplementary neurogenesis and cognitive support.
Selank
SynergisticDifferent mechanisms for anxiety and mood support.
Dihexa
SynergisticComplementary neuroplasticity pathways.
BPC-157
CompatibleDifferent mechanisms, no contraindications.
Timeline
Typical week-by-week effects reported in clinical and observational data.
- Days 1-4
Measurable antidepressant effects in preclinical models
- Weeks 1-2
Neurogenesis and synaptogenesis processes established
- Weeks 2-4
Potential mood and cognitive improvements emerge
- Weeks 4-8
Sustained treatment allows full neurogenic effects
Safety
Reported adverse effects, contraindications, and what to monitor on cycle.
Common side effects
- No effects on TREK-2, TRAAK, TASK-1 channels observed
- No cardiac dysfunction or seizures in preclinical studies
Stop signs — stop and seek advice
- Serotonin syndrome signs
- Severe persistent headaches
- Cardiac symptoms
- Seizure activity
- Severe mood changes or suicidal ideation
Contraindications
- Pregnancy and breastfeeding
- Concurrent MAOI use
Monitoring
- Research compound only - not FDA-approved
- Unknown long-term human effects
- Monitor for serotonin syndrome if combined with serotonergic medications
Quality checks
What a legitimate product looks like, what should give pause, and what should make you stop.
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
Stop signs — don't use
- Cloudy, discolored, or particulate appearance
- Clumped or sticky powder indicating moisture damage
References
Primary literature and clinical-trial data informing this entry.
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.
Last updated . How this page was sourced is described in the methodology.