PE-22-28
PE-22-28 (Optimized Spadin Analog)
TREK-1 Inhibitor for Cognitive Health
The information on this page is compiled from peer-reviewed research and is provided for educational and research purposes only. It is not medical advice, a diagnosis, or a treatment recommendation. Peptides discussed here may not be approved for human use in your jurisdiction. Always consult a qualified healthcare provider before starting, stopping, or modifying any health protocol.
What is PE-22-28?
PE-22-28 is a synthetic heptapeptide (seven amino acids) developed as an optimized analog of spadin, a naturally occurring peptide derived from the propeptide of the TREK-1 potassium channel. Spadin was identified in the early 2010s as an endogenous antidepressant-like molecule, but its short duration of action (approximately 7 hours) and relatively low receptor affinity limited its therapeutic potential. PE-22-28 was engineered to address these limitations, achieving superior TREK-1 channel binding affinity, extended action duration (up to 23 hours), and improved in vivo stability [1].
The primary target of PE-22-28 is the TREK-1 channel (TWIK-related potassium channel 1), a two-pore-domain potassium channel expressed abundantly in neurons of the hippocampus, cortex, and other brain regions relevant to mood and cognition. TREK-1 channels regulate neuronal excitability by controlling potassium ion flow across the cell membrane. When TREK-1 is overactive, it hyperpolarizes neurons and dampens neurotransmitter release, contributing to a state associated with depressive behavior. PE-22-28 binds to and inhibits TREK-1, reversing this hyperpolarization and restoring more normal patterns of neuronal excitability and neurotransmitter signaling.
Preclinical research has generated compelling behavioral data. Mice with TREK-1 gene knockout are resistant to depressive-like states in standard models including the forced swimming test and tail suspension test. PE-22-28 and related spadin analogs replicating TREK-1 inhibition produced significant reductions in immobility time in the forced swimming test, a validated behavioral marker of antidepressant activity. Research published in a PMC peer-reviewed study confirmed that PE-22-28 displayed a better TREK-1 specificity and affinity (IC50 of 0.12 nM) compared to the parent molecule spadin (IC50 40-60 nM) [1].
Beyond mood regulation, PE-22-28 has shown neurogenic effects. It appears to stimulate adult hippocampal neurogenesis within a few days of treatment, promoting the formation of new neurons in a brain region critical for memory encoding, pattern separation, and emotional regulation. Multiple behavioral paradigms have shown improvements in memory formation, learning ability, and recall in rodents treated with TREK-1 inhibitors, suggesting relevance to conditions beyond depression including age-related cognitive decline.
Research Supply
Source high-purity PE-22-28 for your research
Dosage Guide
Route: Subcutaneous injection
Dosing Schedule
| Period | Dose |
|---|---|
| Preclinical rodent protocol | 3.0 mcg/kg subcutaneous for 4 days |
| Investigational human range | 0.5-2 mg subcutaneous per administration, daily or every other day for 2-4 weeks |
Reconstitution
Injection Volumes
| Dose | Volume | Syringe Units |
|---|
Administration Tips
- Reconstitute lyophilized PE-22-28 with bacteriostatic water to the desired concentration
- Store reconstituted peptide at 2-8 degrees Celsius and use within 30 days of reconstitution
- Duration of action is up to 23 hours per dose, supporting once-daily administration
- Human clinical dosing has not been established; all protocols are from preclinical research or investigational reports
Risks & Side Effects
Commonly Reported
Serious Risks
Cardiovascular effects from TREK-1 inhibition
TREK-1 channels are expressed in cardiac tissue; inhibition could theoretically affect cardiac rhythm at high doses.
Excessive neuronal excitability
CNS effects at suprapharmacological doses could result if TREK-1 is inhibited beyond the optimal therapeutic range.
Drug interactions with potassium channel modulators
Interaction with other potassium channel-modulating drugs may produce additive or antagonistic effects.
Unknown long-term neurological consequences
The long-term consequences of sustained adult hippocampal neurogenesis stimulation have not been characterized.
Contraindications
- Cardiac arrhythmia or known channelopathy (TREK-1 channel activity in cardiac tissue; safety unknown)
- Concurrent use of antiarrhythmic drugs affecting potassium channels
- Bipolar disorder (stimulation of neurogenesis and neuronal excitability may destabilize mood in bipolar individuals)
- Pregnancy or breastfeeding (no data; CNS-active agents are generally avoided)
- Known hypersensitivity to PE-22-28 or any component of the formulation
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LEGAL DISCLAIMER
The information provided on this page is for educational and informational purposes only and is not intended as medical advice. PE-22-28 has not been approved by the FDA for any medical condition. Always consult with a qualified healthcare professional before starting any peptide therapy. Individual results may vary. Peptides Institute is not responsible for any adverse effects resulting from the use of information provided on this site.
Frequently Asked Questions
What is PE-22-28 and how does it work?
Does PE-22-28 promote new brain cell growth?
How does PE-22-28 compare to traditional antidepressants?
What is the PE-22-28 dosage?
What are PE-22-28 side effects?
Is PE-22-28 safe for people with bipolar disorder?
References
- Djillani A, Pietri M, Mazella J, et al.. Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity. Front Pharmacol. 2017. PMID 28955242
- Mazella J, Petrault O, Lucas G, et al.. Spadin, a sortilin-derived peptide, targeting rodent TREK-1 channels: a new concept in the antidepressant drug design. PLoS Biol. 2010. PMID 20405001
- Djillani A, Mazella J, Heurteaux C, et al.. Fighting against depression with TREK-1 blockers: Past and future. A focus on spadin. Pharmacol Ther. 2019. PMID 30291907