Nootropics & Neuroprotection
CAS
1801959-12-5
Molecular Weight
774
Da
An early-stage, lab-only peptide that blocks the TREK-1 potassium channel and produces fast antidepressant-like effects in mice. Interesting bench science, no human testing, and almost all of it from a single research group.
Injectable
Intranasal Suitable
Uncertain
Research Compound
PE-22-28 sits in the more experimental, early-adopter corner of the nootropics community, discussed as a novel-mechanism antidepressant rather than a recreational or performance compound. Interest centers on the fast-acting, ketamine-adjacent framing (rapid antidepressant effect via a non-monoamine route) and on neurogenesis claims. The recurring sober note in those threads is honest about how thin the evidence is: rodent-only, single-lab, no human data, which is exactly the gap the Weak score is meant to make legible. The novelty of the mechanism is genuine; the validation is not yet there.
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PE-22-28 is a synthetic heptapeptide derived from spadin, a naturally occurring fragment of the TREK-1 channel propeptide. Spadin showed antidepressant-like activity but degraded quickly; PE-22-28 was engineered from spadin's blood breakdown products to keep the TREK-1 activity while lasting longer in the body. Its name comes from its position as residues 22 to 28 of the parent spadin sequence.
PE-22-28 is a potent, selective blocker of the TREK-1 channel (a two-pore-domain potassium channel) with sub-nanomolar affinity. TREK-1 normally provides a "leak" potassium current that stabilizes neurons at rest; blocking it raises neuronal excitability and, in the dorsal raphe, enhances serotonergic transmission. In rodent models this maps onto rapid antidepressant-like behavior plus increased hippocampal neurogenesis and synaptogenesis, a mechanism distinct from conventional monoamine-reuptake antidepressants.
Studied preclinically for depression, with secondary interest in anxiety, neurogenesis, and cognition. In the research-chemical market it is sold and discussed as a fast-acting mood and neuroplasticity compound. There is no human clinical evidence; all efficacy data are from rodent behavioral models and cell-based electrophysiology.
No human safety data exist. Because the mechanism raises neuronal excitability, theoretical concerns include seizure-threshold effects, and the consequences of TREK-1 blockade in humans are simply unknown. As an unstudied research peptide sold on the gray market, contamination and dosing accuracy are additional real concerns. This is an experimental compound with no established safety profile.
Supplied as a lyophilized powder for reconstitution and parenteral administration in research; subcutaneous and intraperitoneal routes are used in animal studies, and the peptide can cross the blood-brain barrier in those models. Oral bioavailability is negligible. It is sold strictly as a research chemical "not for human consumption."
PE-22-28 is not approved for human use anywhere and has no clinical development program on record. It is sold as a research chemical labeled "not for human consumption." Its CAS registry status has been ambiguous: PeptideClear previously logged it as unassigned (PubChem CID 165437303). A CAS of 1801959-12-5 now appears on at least one chemical-vendor listing (MedChemExpress); this has not been independently confirmed across registry sources and should be verified before being published as authoritative.
pubmed.ncbi.nlm.nih.gov/28955242
https://pubmed.ncbi.nlm.nih.gov/20405001/
Semax, Selank, DSIP
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