PE-22-28
Also known as: Spadin analog, Antidepressant peptide PE-22-28
Overview
PE-22-28 is a synthetic pentapeptide analog of spadin, a naturally occurring peptide derived from the pro-region of the NTSR3/sortilin receptor. Spadin was identified as an endogenous blocker of TREK-1 (TWIK-related potassium channel-1) channels, which are implicated in the mechanism of action of antidepressants. PE-22-28 is a modified, more stable version of spadin with improved pharmacokinetic properties. It has demonstrated rapid antidepressant-like effects and neuroplasticity-promoting properties in preclinical models, with an onset of action measured in hours rather than the weeks required by traditional antidepressants.
Mechanism of Action
PE-22-28 acts as a TREK-1 channel blocker. TREK-1 is a two-pore domain potassium channel that maintains neuronal hyperpolarization; its blockade leads to increased neuronal excitability in serotonergic and dopaminergic circuits. Additionally, PE-22-28 activates the mTOR pathway and CREB transcription factor phosphorylation, promoting BDNF expression and synaptogenesis. It has been shown to increase serotonergic and dopaminergic tone in the prefrontal cortex, hippocampus, and raphe nuclei. Crucially, effects appear within hours in preclinical models rather than requiring weeks of treatment.
Potential Benefits
- Rapid antidepressant-like effects within hours of administration
- TREK-1 blockade improving serotonergic and dopaminergic tone
- Neuroplasticity and synaptogenesis via BDNF upregulation
- mTOR pathway activation supporting neuronal growth
- Potential advantage over traditional antidepressants (faster onset, fewer side effects in preclinical models)
- Anxiety reduction in preclinical models
Dosage Protocols
The following reflects doses used in published research studies. This is not medical advice. Consult a qualified healthcare professional.
| Typical Range | 100-500 mcg/day (speculative; based on rodent data extrapolation) |
| Beginner | 100 mcg/day |
| Intermediate | 200-300 mcg/day |
| Advanced | 400-500 mcg/day |
| Cycle Duration | 2-4 weeks |
| Cycle Off | 2-4 weeks; human dosing and cycling protocols are not established |
Human dosing is entirely speculative — no clinical trials completed. All protocols are extrapolations from preclinical data. Exercise maximum caution; this is an early-stage research peptide.
Use our Reconstitution Calculator to determine exact syringe units for your protocol.
Routes of Administration
Subcutaneous Injection High — systemic distribution
Most common administration route for research peptides. Inject into abdominal fat, thigh, or upper arm. Rotate sites. standard research dose.
Intramuscular Injection High — with slightly faster onset than SC
Alternative route when deeper delivery or faster absorption is desired. Less commonly used than SC for most research peptides.
Read our full Routes of Administration Guide for detailed comparison of all delivery methods.
Stacking Protocols
Popular research stacks involving PE-22-28:
Nootropic Stack
Combines PE-22-28 with Semax (BDNF/cognition) and Selank (anxiolytic) for balanced cognitive enhancement and stress resilience.
Explore our complete Peptide Stacking Guide for more combinations and safety considerations.
Reconstitution
| Typical Vial Size | 2mg, 5mg |
|---|---|
| BAC Water | 1ml per 2mg vial |
| Storage | Refrigerate at 2-8°C after reconstitution |
| Shelf Life | 28 days refrigerated |
Need exact syringe measurements?
Amino Acid Sequence
Ala-Pro-Leu-Pro-Arg (pentapeptide; specific sequence proprietary/research variant of spadin)
Side Effects & Safety
- Human safety profile not established (no completed clinical trials)
- Theoretical: serotonin syndrome risk if combined with serotonergic drugs
- Potential dopaminergic modulation effects
- No known serious adverse events in rodent studies at research doses
Safety & Contraindications
This information is for educational purposes only. Consult a qualified healthcare provider before using any peptide.
Pregnancy / Lactation
Bleeding Disorders
Active Skin Infection at Injection Site
Pharmacokinetics
| Half-Life | ~30-60 minutes (plasma); CNS effects longer |
|---|---|
| Storage | Store lyophilized peptide at -20°C (long-term) or 2-8°C (short-term, under 30 days). Reconstituted: refrigerate at 2-8°C and use within 28-30 days. Protect from light. Do not freeze reconstituted solution. |
Synergistic Compounds
The following compounds have been studied alongside PE-22-28 for potential complementary or synergistic effects:
Learn More
References & Further Reading
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