PE 22-28

PE-22-28 is an excerpt from a larger peptide. Spadin, itself an offshoot of the protein sortilin, inhibits the potassium channel TREK-1; PE-22-28 is its seven-amino-acid C-terminal piece and does the same job with far more force. In cell assays its half-maximal inhibitory concentration was 0.12 nM, against 40 to 60 nM for spadin.

TREK-1 belongs to the two-pore-domain potassium channels and is treated by the literature as a central link in the development of depressive states. Mice without a working TREK-1 gene are shielded from depression-like behaviour. Spadin and its shortened analogs mimic that state pharmacologically.

What the animal models show:

• Spadin's affinity for TREK-1 is 10 nM; in mice it produced a depression-resistant picture across five behavioural tests.
• PE-22-28 shortened the time spent immobile in the swim test and stimulated neurogenesis after four days.
• The effects are linked to stronger serotonergic transmission, more BDNF and increased neuronal plasticity.
• In some papers the effect set in faster than with classical serotonergic substances, which makes the TREK-1 route mechanistically distinct.
• A safety study on spadin found that the remaining functions governed by TREK-1, among them pain, epilepsy and ischemia, were untouched in rodents; related potassium channels were not inhibited, and blood pressure and heart rate did not change.

The literature on PE-22-28 itself starts in 2014 and remains almost entirely preclinical. In the animal models the peptide is mostly given nasally, much like Selank and Semax.

The studies that exist rate PE-22-28 as well tolerated, but nearly all of the data come from animal experiments. What you should keep in mind:

• Nasal mucosa: mild burning or irritation is the most common observation, because the models deliver the peptide nasally.
• Intervention in mood systems: blocking TREK-1 reaches into serotonergic and mood-related pathways, so changes in drive and mood are to be expected.
• Young literature: publications on the peptide itself only go back to 2014, and the safety profile rests almost entirely on rodent data.
• Humans: robust human studies and long-term observations do not exist.

This summary is no substitute for medical advice.

• Spadin, a sortilin-derived peptide, targeting rodent TREK-1 channels: a new concept in the antidepressant drug design - the first description of spadin as a TREK-1 blocker with a depression-resistant phenotype in mice.
• Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity - introduces PE 22-28 as a shortened spadin analog with stronger channel inhibition, better stability and behavioural effects.
• Spadin as a new antidepressant: absence of TREK-1-related side effects - safety data on spadin in rodents: pain, epilepsy, ischemia, blood pressure and heart rate were unaffected.