PE-22-28
Synthetic peptide derived from spadin. TREK-1 channel inhibitor with rapid antidepressant effects in animal models. Pre-clinical.
PE-22-28: Synthetic peptide derived from spadin. TREK-1 channel inhibitor with rapid antidepressant effects in animal models. Pre-clinical. PE-22-28 is derived from spadin and blocks the TREK-1 channel.
PE-22-28 is derived from spadin and blocks the TREK-1 channel. Animal-model antidepressant effects in days rather than weeks. Pre-clinical only, no human dose protocol, real interactions with SSRIs / SNRIs / heart-arrhythmia drugs.
Who it's for
- →Researchers studying TREK-1 pathways
- →Antidepressant-mechanism research
- →Educational reference, limited human safety data
What to expect
- Week 1
Animal models show mood-task improvements rapidly.
- Week 4
Cycle endpoint in pre-clinical protocols.
- Week 8
No human long term data.
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How it works (mechanism)
TREK-1 channel inhibitor derived from spadin. TREK-1 is a potassium channel involved in mood regulation; blocking it produces fast antidepressant effects in animal models.
Dosing protocol
Stacks well with
Side effects
When NOT to use
- ⚠Active SSRI / SNRI / MAOI regimens
- ⚠Cardiac arrhythmia history
- ⚠Pregnancy / nursing
Common mistakes
- • Stacking with other mood-active compounds
- • Long cycles without safety data
- • Treating animal-model dose as human dose
What it actually is
PE-22-28 is a fragment of spadin, itself a fragment of the sortilin propeptide. It blocks the TREK-1 potassium channel, and blocking TREK-1 produces antidepressant effects in animals within days rather than the weeks conventional antidepressants take. It is preclinical: zero human trials, and no human dosing protocol.
TREK-1 is a potassium channel that influences neuronal excitability, and mice lacking it show a depression-resistant phenotype. Blocking the channel pharmacologically reproduces that, with antidepressant-like behavioural effects appearing in rodents within about four days. The comparison usually drawn against the weeks conventional antidepressants take in humans is a cross-species one and does not hold as stated. The mechanism is genuinely different from serotonin reuptake inhibition, which is why it is interesting. TREK-1 is also expressed in cardiac tissue, which is where the theoretical caution comes from. It cuts both ways: PE-22-28 analogues did not inhibit hERG in testing, and parent spadin studies reported no detected cardiac dysfunction or blood-pressure effect in the models tested.
Forms, and which is which
Animal-model dosing is per kilogram and not translatable. No human protocol exists.
Verdict: The honest description of where this is.
Used in some animal work as a route to the brain for a short peptide.
Verdict: A plausible route, untested in people.
Buyer reconstitutes at an extrapolated dose. No brain-exposure data in humans.
Verdict: Unverified material, invented dose.
Conventional antidepressants, psychotherapy and, for treatment-resistant cases, ketamine and esketamine all have real randomised evidence.
Verdict: The comparison anyone with a diagnosis should make first.
What it is claimed to do, graded
Demonstrated in animal models within days, which is the whole interest. Zero human trials.
A 2019 paper reported the first evidence of protective effects in a stroke model. Preclinical.
Reported for sortilin-derived peptides in a 2021 study. A different tissue and a separate line of work.
No human safety data. TREK-1 is expressed in cardiac tissue, so effects on the heart are a specific rather than generic concern, and nobody has measured them in a person.
Grades describe how much human evidence exists for that specific claim, not whether it will work for you or whether it is safe.
Pros and cons
- • A genuinely novel antidepressant mechanism, distinct from anything currently approved
- • The rapid onset in animal models is the interesting part — days rather than weeks
- • Published in reputable journals with a coherent line of work behind it
- • Zero human trials — grade D on the site's own ladder
- • TREK-1 is expressed in the heart, so cardiac effects are a specific untested concern
- • No human dosing protocol, so any dose offered was invented
- • Marketed for depression, a condition where self-treating with an untested compound carries serious risk
- • Research-chemical supply with unverified identity
When to stop
- • Palpitations, chest discomfort or any irregular heartbeat
- • Mood worsening, or any thought of self-harm — get help, and 988 is the US crisis line
- • Injection-site reaction that spreads
- • Honestly: before starting, if you are treating diagnosed depression — talk to a clinician
Interactions
Not a characterised pharmacological interaction — the reason is that adding an untested compound to treatment for a serious condition, with no data in either direction, is not something to work out on yourself.
TREK-1 is expressed in cardiac tissue. This is the specific concern, not a generic caution.
Listed because both classes touch cardiac ion channels, which is not the same target. No interaction data exists in either direction.
The most important line here. Depression has treatments with real evidence, and this has none.
There is no human interaction literature for this compound.
Is this for you?
- • Laboratory research. There is no human context for this compound
- • You take an SSRI, SNRI or MAOI
- • You have any history of cardiac arrhythmia
- • You are treating diagnosed depression and would be using this instead of care
- • You are pregnant or nursing
The one number
Sources for the claims above
- First evidence of protective effects on stroke recovery and post-stroke depression
- Sortilin-derived peptides promote pancreatic beta-cell survival
- Sortilin-derived propeptide regulation during adipocyte differentiation
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Tracked alongside PE-22-28
Same goal, different aisle — each graded on its own evidence in the Pepdex catalog.
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