PE-22-28
Spadin-derived peptide
Targeting TREK-1 for faster antidepressant action.
Half-life
~ short (minutes; stabilized analogs extend this)
Mol. weight
2012.3 g/mol (C96H142N26O22)
Sequence
Gly-Val-Ser-Trp-Gly-Leu-Arg (GVSWGLR)
Discussions
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Overview
A peptide derived from spadin, itself derived from the maturation of sortilin/sortilin-related proteins, that blocks the TREK-1 (TWIK-related potassium channel-1) channel. Blocking TREK-1 is associated with enhanced serotoninergic neurotransmission and rapid antidepressant-like effects in preclinical models, positioning PE-22-28 as a research candidate for fast-onset mood modulation.
Mechanism of action
PE-22-28 blocks the TREK-1 potassium channel. TREK-1 sets the resting membrane potential of some serotonergic neurons; blocking it increases their excitability and enhances serotoninergic neurotransmission. In preclinical models, TREK-1 knockout animals are resistant to depression-like behavior, and TREK-1 blockade produces rapid antidepressant-like effects — the rationale linking PE-22-28 to fast-onset mood modulation distinct from slow-onset SSRI mechanisms.
Researched benefits
- Blocks TREK-1 to enhance serotonergic signaling
- Rapid antidepressant-like effects in preclinical models
- Distinct, fast-onset mechanism vs SSRIs
Considerations
- Preclinical; no human data
- Not approved for human use
- Research context only
Key Academic Literature & Studies
Search more in PubMedPeer-reviewed citations and clinical trials evaluating PE-22-28 in scientific literature.
Query PubMed for recent peer-reviewed preclinical and clinical publications on PE-22-28:
View PE-22-28 index on PubMed (NCBI)