PE-22-28
Spadin Analog (PE-22-28)
Fast-acting antidepressant peptide via TREK-1 channels
PE-22-28 is a synthetic analog of spadin that blocks TREK-1 potassium channels. Research shows antidepressant effects within 4 days versus weeks for SSRIs.
Admin routes
Intranasal, Subcutaneous
Popularity
Niche
Side effects
Generally mild
AU vendors
0 rated
✓Key benefits
📈What to expect
Rapid mood improvement (vs 2–4 weeks for SSRIs)
Stabilised mood; reduced anxiety and rumination
Enhanced cognitive function alongside mood benefits
Sustained antidepressant effects with neurogenesis
Based on community reports and published research. Individual results vary significantly.
💊Dosing protocols
Mood support (intranasal)
100–200 mcg
Once daily
4–8 weeks
Subcutaneous
100 mcg
Once daily
4–8 weeks
Dosing information is sourced from published research and community protocols. This is not a recommendation. Consult a healthcare professional.
Research status|Preclinical - animal studies only
Overview
PE-22-28 is a synthetic heptapeptide analog of spadin, a natural peptide derived from sortilin. It acts by blocking TREK-1 (TWIK-related potassium channel 1), a potassium channel that is strongly linked to depression. TREK-1 knockout mice exhibit depression-resistant behaviour, and blocking this channel mimics that effect. In animal studies, PE-22-28 produces antidepressant effects within 4 days, compared to 2–4 weeks for traditional SSRIs.
⚙️How it works
Blocks TREK-1 potassium channels in the brain. TREK-1 channels, when overactive, reduce neuronal excitability in mood-regulating circuits. By inhibiting TREK-1, PE-22-28 increases serotonergic neurotransmission, promotes neurogenesis in the hippocampus, and enhances BDNF expression - all mechanisms associated with antidepressant action, but achieved through a novel target.
⚡Side effects
📅Research history
Spadin identified as TREK-1 antagonist with antidepressant properties
PE-22-28 developed as more stable, potent spadin analog
Review of TREK-1 as antidepressant target published
Growing interest in nootropic and mental health peptide communities
A new antidepressant mechanism
Traditional antidepressants (SSRIs, SNRIs) work by modulating serotonin and/or norepinephrine reuptake. PE-22-28 targets a completely different system - potassium channel conductance. This is significant because approximately 30% of depressed patients don't respond to SSRIs. A novel mechanism could potentially help treatment-resistant cases. However, all data is from animal models - human trials have not been conducted.
References
- [1]Mazella J, et al. 'Spadin, a sortilin-derived peptide, targeting TREK-1 channel: a new concept in the antidepressant drug design.' PLoS Biology, 2010.
- [2]Djillani A, et al. 'Role of TREK-1 in health and disease, focus on the central nervous system.' Frontiers in Pharmacology, 2019.
Frequently asked questions
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Open CalculatorDisclaimer: This guide is for educational and informational purposes only. It is not medical advice. The dosing protocols listed are sourced from published research and community reports and do not constitute a recommendation. Always consult a qualified healthcare professional before using any peptide. Australian regulations classify many peptides as Schedule 4 (prescription-only) substances. Check current TGA guidelines before purchasing.