PE-22-28

In simple words

PE-22-28 is a short peptide of seven amino acids, a shortened version of the natural peptide spadin. It is studied in animals as a possible fast-acting agent against depression.

What this molecule is

A 7-amino-acid shortened fragment of spadin. IC₅₀ = 0.12 nM (vs 40 nM for spadin — 300 times more potent). ~858 Da.

Why it is studied

TREK-1 blocker (two-pore K⁺ channel) → antidepressant effect within 4 days (vs 3-4 weeks for SSRIs in mice). ↑neurogenesis in the hippocampus. Potential in treatment-resistant depression. Preclinical only so far.

How it works

TREK-1 (KCNK2) blockade → ↑excitability of serotonergic neurons of the DRN → ↑serotonin + ↑neurogenesis (dentate gyrus of the hippocampus). ↑PSD-95 (synaptogenesis). Effect after 4 days (uniquely fast).

Doses used in studies

Researchers' practice describes 100-500 mcg intranasally or SC. Not validated. Animal data only.

Combined with in studies

• Semax — serotonin + dopamine, different mechanisms
• Selank — anxiolysis — complementary
• NOT with SSRIs/MAOIs — serotonin potentiation

Level of evidence

Level C Animal studies. Effects have been shown in animals. Whether they carry over to humans has not been proven. animals only. No clinical data.

Important to know

⚠️ Found in confiscated nootropics (gray market). TREK-1 is expressed in the heart/GI tract/kidneys — peripheral effects are unknown. Combination with antidepressants is contraindicated. Research only.

Studies in PubMed

1. Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity. (Front Pharmacol, 2017)
2. Spadin, a sortilin-derived peptide, targeting rodent TREK-1 channels: a new concept in the antidepressant drug design. (PLoS Biol, 2010)
3. In vitro and in vivo regulation of synaptogenesis by the novel antidepressant spadin. (Br J Pharmacol, 2015)
4. Fighting against depression with TREK-1 blockers: Past and future. A focus on spadin. (Pharmacol Ther, 2019)
5. First evidence of protective effects on stroke recovery and post-stroke depression induced by sortilin-derived peptides. (Neuropharmacology, 2019)
6. The occurrence of putative cognitive enhancing research peptides in seized pharmaceutical preparations: An incentive for controlling agencies to prepare for future encounters of the kind. (Drug Test Anal, 2020)