Summary
PE-22-28 is a shortened analog of spadin, a natural peptide that blocks the TREK-1 potassium channel. TREK-1 knockout mice resist depression-like behaviour, and spadin produced fast antidepressant-like effects in mice. The shorter analogs were designed to last longer while keeping that activity.
Structure
A shortened, stabilized analog of spadin, a peptide derived from the propeptide of sortilin.
How it works
Blocking TREK-1 increases serotonergic neuron firing and promotes hippocampal neurogenesis in mice, within days rather than the weeks typical of SSRIs.
Research use cases
Areas where PE-22-28 has been studied. Inclusion here does not mean it works for that purpose.
- Depression models
- Neurogenesis research
What the research found
Spadin
Spadin blocked TREK-1, increased serotonin neuron firing and induced antidepressant-like behaviour and neurogenesis in mice after four days.1
Shortened analogs
Truncated spadin analogs retained TREK-1 blockade and antidepressant-like effects in mice with improved stability.2
Safety and open questions
No human data.
Regulatory status
Preclinical. Sold for research use.
Status was accurate when this page was last reviewed on October 26, 2026. Regulations change; check with the relevant authority before relying on it.
PE-22-28: common questions
Has PE-22-28 been tested in people?
No published human studies exist as of our last review.
Is PE-22-28 approved for human use?
Preclinical. Sold for research use.
References
- Mazella J, Pétrault O, Lucas G, et al. (2010). Spadin, a sortilin-derived peptide, targeting rodent TREK-1 channels: a new concept in the antidepressant drug design. PLoS Biology.
- Djillani A, Pietri M, Moreno S, et al. (2017). Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity. Frontiers in Pharmacology.
Links open a PubMed search for the exact title, or the original source where one is given.