Seven-amino-acid fragment of the antidepressant peptide spadin that blocks the TREK-1 potassium channel; tested only in mice.
Also called Mini-spadin, PE 22-28, Spadin analog
PE-22-28 is a seven-amino-acid peptide (Gly-Val-Ser-Trp-Gly-Leu-Arg) cut from spadin, a fragment of the propeptide released when cells make the sortilin receptor. Mice bred without TREK-1, a potassium channel in neurons, behave as if they were on antidepressants. In 2010 a French CNRS group led by Jean Mazella and Marc Borsotto showed that spadin blocks TREK-1 and has antidepressant-like effects in mice.
In 2017 the same group showed the shorter PE-22-28 blocked human TREK-1 in cells far more strongly than spadin (IC50 0.12 nM vs 40-60 nM). In mice it cut immobility in the forced swim test, shortened the time to eat in the novelty-suppressed feeding test after 4 days, and increased new neurons in the hippocampus. Modified versions kept working for up to about 23 hours instead of spadin's 7.
That is the entire evidence base: mouse behavior tests and cell recordings from one research group. No human has received PE-22-28 or spadin in a published study, and there is no registered trial. The intranasal sprays sold for anxiety, mood or focus are untested in people.
What it binds to, and what happens inside the body after that, step by step.
TREK-1 is a two-pore-domain potassium channel that keeps neurons quiet by letting potassium leak out. Blocking it makes serotonin neurons in the dorsal raphe fire more, which is one of the things standard antidepressants do slowly. In mice, spadin and PE-22-28 produced antidepressant-like behavior and new hippocampal neurons within 4 days rather than the 3 weeks needed for fluoxetine.
Human results and animal results are kept apart below. A result in rats tells you a mechanism is plausible. It does not tell you what happens in a person.
Everything known comes from mouse behavior tests and channel recordings in cells, all from one French research group. The mouse results are consistent and the channel data are clean, but forced-swim and feeding tests are screening tools that many failed antidepressant candidates have passed. There is no human data on effect, dose or safety.
No human studies are among the key studies for PE-22-28. Everything known comes from animals or cells.
Human TREK-1 expressed in HEK cells; mice in forced swim and novelty-suppressed feeding tests
PE-22-28 blocked TREK-1 with an IC50 of 0.12 nM vs 40-60 nM for spadin, cut forced-swim immobility, increased neurogenesis after 4 days, and modified analogs worked for up to 23 hours vs 7 for spadin.
Read the studyMice with experimental focal brain ischemia
Mini-spadin had a two-sided effect on TREK-1 (activating at low dose, blocking at high dose), improved motor and cognitive deficits after stroke, and prevented depression-like behavior.
Read the studyMice in five antidepressant behavior tests; mouse neurons and brain slices
Spadin bound TREK-1 at 10 nM, increased serotonin neuron firing, and gave antidepressant-like effects and neurogenesis after 4 days of IV treatment.
Read the studyMice and rats tested for pain, seizures, ischemia, cardiac function and glucose
Spadin did not change pain sensitivity, seizure threshold, stroke size, heart rhythm, blood pressure or blood sugar, and did not block other K2P channels.
Read the studyMice
Two reversed-sequence spadin analogs kept antidepressant-like effects and neurogenesis after 4 days without pain, seizure or cardiac side effects.
Read the studyThese are questions the published research has not answered.
No product containing PE-22-28 is approved as a medicine by the FDA.
Preclinical only; no registered human trial of PE-22-28 or spadin on ClinicalTrials.gov and no published human results. Not named on the WADA list; as a substance with no government approval for human use it falls under WADA class S0 (non-approved substances), banned at all times.
No human half-life has been published for PE-22-28, so we do not draw a clearance curve. Half-lives quoted online for it are usually estimates from animal data.
No human study or approved label has published a dose for PE-22-28, so there is no table to show.
No dose of PE-22-28 has been tested in a published human study or approved on a label. Numbers that circulate online come from animal studies scaled up by guesswork or from sellers. We do not reproduce them.
Which symptoms are expected and which mean stop and get help: side effects and red flags.
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It produced antidepressant-like behavior in mice within 4 days. Mouse forced-swim results have a poor record of predicting human antidepressant effects, and no human study exists.
Short rodent studies of the parent peptide spadin found no pain, seizure or heart effects. No safety study has been done in people.
Its parent, spadin, is a fragment of a natural propeptide found in mouse and human serum. PE-22-28 is a shorter synthetic fragment and is usually sold with chemical modifications.
The published studies used injections in mice. No study has measured brain levels after nasal use.
These pairings come up often. Almost none have been tested together in a trial, and the evidence note on each says so plainly.
No published stability data exist for the research-grade powder. Research suppliers generally ship it as a freeze-dried powder and list frozen storage (-20 C), dry and away from light; none of this has been independently verified.
No published stability data exist for a reconstituted solution. The usual lab practice for small peptides is refrigeration at 2-8 C and short use windows, but no study has tested how long this compound stays intact once mixed.
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