PE-22-28

Also known as: Spadin Analog; TREK-1 Inhibitor

Overview

PE-22-28 is a spadin-derived peptide that blocks TREK-1 potassium channels implicated in mood and cognition. It shows rapid antidepressant effects, increases neurogenesis within days, and supports synaptic plasticity with fewer side effects than traditional antidepressants.

Benefits

- Mood support

- Cognitive enhancement

- Stroke recovery

- Neuroprotection

Consider This Peptide If You Want To

- Support mood regulation and reduce anxiety/depression

- Enhance cognition and neuroprotection

Dosage & Administration

Dosage Guidelines

Recommended Dosage

• Amount:400 mcg

• Frequency:daily

• Duration:4 weeks

• Rest Period:4 weeks

• Time of Day:morning

• Ingestion:intranasal

Administration Routes:Intranasal

Research Findings on Dosage:

Nasal Spray:

- **Commonly Reported Dosage:** 400 mcg once per day in the

morning

Mechanism of Action

How this peptide works in the body

TREK-1 Channel Inhibition:

PE-22-28 blocks TREK-1 potassium channels, reducing potassium (K⁺) efflux from neurons, which stabilizes membrane potential and increases neuronal excitability. This enhances resistance to stress-induced dysfunction by preventing excessive neuronal hyperpolarization.

Neurogenesis:

PE-22-28 promotes the proliferation and differentiation of neural progenitor cells in the hippocampus by upregulating brain-derived neurotrophic factor (BDNF) and activating the Wnt/β-catenin signaling pathway. This supports neural regeneration and cognitive enhancement.

Synaptic Plasticity:

PE-22-28 enhances dendritic spine density and modulates NMDA receptor activity, improving synaptic strength and learning capacity. It also increases calcium (Ca²⁺) influx via NMDA receptor trafficking, reinforcing long-term potentiation (LTP) and memory formation.

Mood Stabilization:

PE-22-28 regulates serotonin (5-HT) and dopamine (DA) neurotransmission by modulating monoaminergic pathways influenced by TREK-1 inhibition. This contributes to rapid antidepressant effects without the side effects of traditional antidepressants.

Inflammation Modulation:

PE-22-28 reduces neuroinflammation by suppressing pro-inflammatory cytokines (IL-6, TNF-α) and mitigating oxidative stress. This protects neurons from inflammatory damage and supports overall brain health.

Consider Stacking With

- Any GHRP (Ipamorelin, Hexarelin)

- Any GHRH (CJC-1295, MOD-GRF-1295, Tesamorelin)

- BPC-157

- TB-4

- Oxytocin

- FGL(L)

- Selank

- Semax

- Cerebrolysin

Side Effects & Cautions

Common Side Effects

- Well tolerated; no side effects reported

Research & References

Research Highlights

Rapid Antidepressant Effects:

Reduced depressive-like behaviors in mice after four days of treatment in the Forced Swimming Test and Novelty Suppressed Feeding Test.

Stroke Recovery:

Long-term improvements in neurogenesis, learning capacity, and motor coordination, observed up to ten weeks post-ischemia in animal models.

Neurodegeneration:

Demonstrated potential in mitigating cognitive decline and improving neural plasticity in preclinical studies.

References

"Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity."

"Spadin and Shortened Spadin Analogs as Efficient New Antidepressants in Mouse Models of Post-Stroke Depression."

"Spadin and Its Analogs Improve Recovery After Stroke by Preventing Post-Stroke Depression."

Proceedings from the 7th International Conference on Neurological Disorders & Stroke