PE-22-28
Emerging researchTREK-1 Channel Blocker | Shortened Spadin Analog
Synthetic heptapeptide derived from Spadin positions 22-28, functioning as potent TREK-1 antagonist with enhanced selectivity and duration versus parent compound.
Molecular & research data
- Sequence
- Gly-Val-Ser-Trp-Gly-Leu-Arg (GVSWGLR)
- Molecular weight
- 773.89 Da
- Half-life
- Approximately 23 hours
- Primary targets
- serotonin-receptor
- Routes (research)
- Injectable, Oral, Nasal
- Storage
- Refrigerate at 2-8°C, use within 4-6 weeks
Overview
Synthetic heptapeptide derived from Spadin positions 22-28, functioning as potent TREK-1 antagonist with enhanced selectivity and duration versus parent compound. Primary research focus on rapid antidepressant effects.
Mechanism of action
Selectively blocks TREK-1 potassium channels (IC50: 0.12 nM). Enhances serotonin neurotransmission in dorsal raphe nucleus, triggering CREB activation and hippocampal neurogenesis.
Key research findings
- Rapid antidepressant effects within 4 days (preclinical)
- Hippocampal neurogenesis and synaptogenesis
- Enhanced serotonergic neurotransmission
- Extended ~23 hour duration of action
- 300-500x greater potency than full-length Spadin
Research applications
Mental Health
- Depression — Primary research focus with rapid effects in behavioral models within 4 days.
- Anxiety — Anxiolytic properties demonstrated in preclinical anxiety models.
Neurogenesis
- Hippocampal Neurogenesis — Nearly doubles BrdU-positive cells after 4-day treatment.
- Synaptogenesis — Promotes new synapse formation through CREB activation.
Cognition
- Memory Support — Hippocampal and prefrontal cortex TREK-1 expression supports memory.
- Neuroprotection — Potential ischemic protection and neuronal survival support.
PE-22-28 FAQ
How much more potent is PE-22-28 compared to full-length Spadin?+
PE-22-28 is dramatically more potent—roughly 300-500x more potent than full-length Spadin. This extraordinary difference comes from being a shortened fragment that better mimics the active site. The result is an IC50 of just 0.12 nM for TREK-1 inhibition versus 40-60 nM for Spadin.
Can PE-22-28 work as a standalone antidepressant, or is it just for research?+
PE-22-28 shows rapid antidepressant effects in animal models (within 4 days), but it's currently research-only with no human clinical trials completed. It's not approved for therapeutic use. However, the preclinical evidence is strong enough that clinical development may follow if pharmaceutical companies invest in it.
How long does PE-22-28's effect on neurogenesis last?+
In preclinical studies, neurogenesis and synaptogenesis establishment begins within 1-2 weeks of treatment. However, we don't know how long effects persist after discontinuation—that depends on sustained CREB activation and whether new neurons survive. Duration data doesn't exist for human use.
Is PE-22-28 safe to combine with SSRIs?+
Caution is advised. Both PE-22-28 and SSRIs enhance serotonin. While the interactions section says to 'monitor,' combining them theoretically increases serotonin syndrome risk. Start carefully with your healthcare provider's supervision if considering this combination. Never combine with MAOIs.
References
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Last reviewed: 2026-06-26. Information is provided for research and educational reference only — see our disclaimer.