Research Only Cognitive & Nootropic

PE-22-28

also known as: PE22-28, spadin

A short peptide that selectively blocks the TREK-1 potassium channel — studied in animal models as a fast-acting antidepressant candidate.

A 7-amino-acid peptide derived from the propeptide of sortilin that selectively inhibits the TREK-1 two-pore potassium channel, producing antidepressant-like effects in rodent models with an onset of hours rather than weeks.

Mechanism of action

Selective blockade of the TREK-1 (TWIK-related potassium-1) channel, a two-pore-domain potassium channel implicated in mood regulation. TREK-1 knockout mice show a depression-resistant phenotype; pharmacological inhibition with PE-22-28 reproduces this phenotype in wild-type rodents, with antidepressant-like effects appearing within hours — substantially faster than SSRIs.

Primary uses

Rodent depression models
TREK-1 channel pharmacology research

Typical dosing

preclinical only varies (IV, IP (preclinical))

No human dosing established. Community use carries unknown risk; not medical guidance.

Regulatory status

Not approved. Preclinical-stage research peptide. No completed human clinical trials identified.

References

[pubmed] Mazella J, et al. "Spadin, a sortilin-derived peptide, targeting rodent TREK-1 channels: a new concept in the antidepressant drug design." PLoS Biol, 2010;8:e1000355.
[pubmed] Djillani A, et al. "Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability, and Antidepressant Activity." Front Pharmacol, 2017;8:643.

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Disclaimer

This entry is for educational purposes only and does not constitute medical advice. Dosing information reflects published regulatory or research data and is not a recommendation. Many compounds described here are not approved for human use in the United States. Consult a licensed medical professional before considering any peptide therapy.