PE-22-28
Also known as: Spadin Analog, PE22-28
PE-22-28 is a synthetic peptide analog of spadin that acts as a TREK-1 potassium channel blocker with potential antidepressant and cognitive enhancement properties. This hexapeptide demonstrates neuroprotective effects through modulation of neuronal excitability and synaptic plasticity.
PE-22-28 is a 604.7 g/mol research peptide. PE-22-28 is a synthetic peptide analog of spadin that acts as a TREK-1 potassium channel blocker with potential antidepressant and cognitive enhancement properties. This hexapeptide demonstrates neuroprotective effects through modulation of neuronal excitability and synaptic plasticity.
Also called: Spadin Analog, PE22-28
604.7 g/mol
Molecular Weight
Daltons
0
Strong Evidence
benefits
4
Studies Cited
peer-reviewed
0.1-0.5
Typical Dose
mg/kg
Overview
PE-22-28 represents a modified version of spadin, a naturally occurring peptide derived from propeptide sortilin. The peptide functions primarily through selective inhibition of TREK-1 (TWIK-related K+ channel 1) potassium channels, which are widely distributed throughout the central nervous system. By blocking these channels, PE-22-28 increases neuronal excitability and promotes depolarization, leading to enhanced neurotransmitter release and improved synaptic transmission. Research indicates this mechanism contributes to antidepressant-like effects comparable to traditional selective serotonin reuptake inhibitors, but through a novel pathway that doesn't directly target monoamine systems. The peptide also demonstrates neuroprotective properties by reducing neuronal apoptosis and promoting cell survival under stress conditions. Studies suggest PE-22-28 may enhance cognitive function through improved hippocampal neurogenesis and increased brain-derived neurotrophic factor expression. Unlike many antidepressant compounds, PE-22-28 shows rapid onset of action, with effects observable within hours rather than weeks of administration.
Key Takeaways: PE-22-28
- Research doses typically range from 0.1 to 0.5 mg/kg via subcutaneous
- 0 benefits with strong evidence, 2 moderate, 3 preliminary
- Half-life: 45-90 minutes
- 4 cited research studies in this guide
Mechanism of Action
PE-22-28 selectively blocks TREK-1 potassium channels, preventing potassium efflux and maintaining neuronal depolarization. This blockade increases neuronal excitability, enhances neurotransmitter release, and promotes synaptic plasticity. The peptide also activates cAMP-PKA signaling pathways, leading to CREB phosphorylation and increased expression of neurotrophic factors including BDNF. Additionally, PE-22-28 modulates HPA axis activity by reducing cortisol release and normalizing stress responses.
Research Benefits
PE-22-28 at a Glance
PE-22-28 selectively blocks TREK-1 potassium channels, preventing potassium efflux and maintaining neuronal depolarization.
Rapid Antidepressant Effects
Moderate EvidencePE-22-28 produces antidepressant-like effects within hours through TREK-1 channel blockade, bypassing traditional monoamine pathways and offering potential treatment for treatment-resistant depression.
Neuroprotection Against Stress
Moderate EvidenceProtects neurons from stress-induced damage by reducing apoptosis, maintaining mitochondrial function, and preventing dendritic spine loss during chronic stress exposure.
Enhanced Cognitive Function
PreliminaryImproves memory formation and retrieval through increased hippocampal neurogenesis and enhanced long-term potentiation, particularly benefiting spatial and working memory tasks.
Improved Neuroplasticity
PreliminaryPromotes synaptic plasticity through BDNF upregulation and enhanced neurogenesis, supporting brain adaptation and recovery from neurological insults.
Anxiolytic Properties
PreliminaryReduces anxiety-like behaviors through modulation of amygdala activity and normalization of stress hormone levels, complementing antidepressant effects.
Enhanced Sleep Quality
AnecdotalImproves sleep architecture by normalizing circadian rhythms and reducing REM sleep disturbances commonly associated with depression and anxiety disorders.
Research Dosing Protocols
Research Purposes Only: All content is for informational and research purposes only. This site does not provide medical advice, diagnosis, or treatment. Consult a qualified healthcare professional before using any peptide or supplement.
| Research Protocol | Dose Range | Route |
|---|---|---|
| Antidepressant research | 0.1–0.5 mg/kg | subcutaneous |
| Cognitive enhancement studies | 1–5 mg | intranasal |
| Neuroprotection research | 0.5–2 mg | subcutaneous |
Frequency
Once daily to twice daily
Timing
Morning administration preferred for cognitive studies, evening for sleep research
Cycle Length
2-4 weeks for acute studies, up to 8 weeks for chronic research
Research Notes
- 1Start with lowest effective dose and titrate based on research endpoints
- 2Intranasal administration may provide better CNS penetration
- 3Monitor for rapid onset effects within 2-6 hours
- 4Research purposes only - not approved for human consumption
Reconstitution Guide
Standard Reconstitution
Vial Size
5 mg
Bacteriostatic Water
2 mL
Concentration
25 mcg
per 0.1 mL (10 units)
Step-by-Step Guide
Gather Materials
PE-22-28 vial, bacteriostatic water, alcohol swabs, insulin syringes.
Equilibrate Temperature
Remove the vial from storage and allow it to reach room temperature (5-10 minutes).
Sanitize
Swab the rubber stopper of both the peptide vial and bacteriostatic water vial with alcohol.
Draw Water
Draw 2 mL of bacteriostatic water into a syringe.
Add Water to Vial
Insert the needle into the peptide vial and direct the water stream against the glass wall — not directly onto the powder.
Mix Gently
Swirl the vial gently until the powder is fully dissolved. Never shake. The solution should be clear and colorless.
Store Properly
Refrigerate at 2-8°C refrigerated. 30 days refrigerated after reconstitution.
Storage Temperature
2-8°C refrigerated
Shelf Life
30 days refrigerated after reconstitution
Important Notes
- •Use bacteriostatic water for multi-dose vials
- •Allow to reach room temperature before injection
- •Gentle mixing - avoid vigorous shaking
- •Store lyophilized powder at -20°C for long-term storage
- •Protect from light during storage and handling
PE-22-28 Dosing Calculator
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PE-22-28 Reconstitution Calculator
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Safety & Side Effects
Reported Side Effects
- !Mild injection site irritation or redness
- !Transient headaches within first few hours
- !Initial sleep pattern changes or vivid dreams
- !Mild nausea or gastrointestinal discomfort
- !Temporary changes in appetite
- !Potential mood fluctuations during adjustment period
- !Dizziness or lightheadedness
- !Fatigue or energy level changes
- !Possible interaction with existing medications
Potential Interactions
- ⚡May potentiate effects of other antidepressant medications
- ⚡Possible interaction with potassium channel modulators
- ⚡Could affect efficacy of anesthetic agents that target ion channels
- ⚡May interact with medications affecting GABA or glutamate systems
- ⚡Potential interaction with neuroprotective supplements
Important: Side effects and interactions listed here are compiled from published research and community reports. This is not a complete list. No formal drug interaction studies have been conducted for most research peptides. Always consult a qualified healthcare provider.
Research Studies
The following studies are referenced in this profile. PubMed IDs are provided where available for independent verification.
TREK-1 channel blockade produces antidepressant-like effects
Demonstrated that TREK-1 channel inhibition produces rapid antidepressant effects in animal models, establishing the therapeutic potential of this mechanism.
Spadin analogs and their antidepressant properties
Investigated structure-activity relationships of spadin analogs including PE-22-28, showing improved stability and maintained antidepressant efficacy.
Neuroprotective effects of TREK-1 channel modulators
Explored neuroprotective mechanisms of TREK-1 inhibitors in models of neuronal stress, revealing enhanced cell survival and reduced apoptosis.
Cognitive enhancement through potassium channel modulation
Examined effects of TREK-1 blockade on hippocampal function and memory formation, demonstrating improved cognitive performance in behavioral tasks.
Note: This is not an exhaustive list of all published research. Studies are selected for relevance and quality. Click PubMed IDs to verify sources independently. Inclusion does not imply endorsement of the peptide for any clinical use.
Frequently Asked Questions
PE-22-28 is a synthetic peptide that blocks TREK-1 potassium channels in the brain, leading to increased neuronal activity and potential antidepressant and cognitive enhancement effects through a novel mechanism.
Research suggests PE-22-28 may produce effects within hours rather than the weeks typically required for traditional antidepressants, due to its direct action on ion channels rather than neurotransmitter reuptake.
Research dosages typically range from 0.1-0.5 mg/kg for subcutaneous administration or 1-5 mg for intranasal delivery, depending on the specific research application and endpoints.
Oral bioavailability of PE-22-28 is poor due to peptide degradation in the digestive system. Subcutaneous injection or intranasal administration are preferred routes for research applications.
Common side effects in research include mild injection site reactions, temporary headaches, sleep pattern changes, and possible mood fluctuations during the initial adjustment period.
Reconstituted PE-22-28 should be stored refrigerated at 2-8°C and used within 30 days. The lyophilized powder can be stored at -20°C for extended periods.
PE-22-28 is available for legitimate research purposes only and is not approved for human consumption or therapeutic use. Check local regulations regarding research peptide purchases.
While research on combinations is limited, PE-22-28 may interact with other compounds affecting ion channels or neurotransmitter systems. Careful consideration and monitoring are essential in research protocols.
Research & Educational Use Only
All content is for informational and research purposes only. This site does not provide medical advice, diagnosis, or treatment. Consult a qualified healthcare professional before using any peptide or supplement.
The information presented here is compiled from published research studies and is intended for informational purposes only. Individual results may vary. Always consult with a licensed healthcare provider.