PE-22-28 (Mini-Spadin)
TREK-1 Channel Blocker · Shortened Spadin Analog
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.
Selectively blocks TREK-1 potassium channels (IC50: 0.12 nM). Enhances serotonin neurotransmission in dorsal raphe nucleus, triggering CREB activation and hippocampal neurogenesis.
Primary research focus with rapid effects in behavioral models within 4 days.
Anxiolytic properties demonstrated in preclinical anxiety models.
Nearly doubles BrdU-positive cells after 4-day treatment.
Promotes new synapse formation through CREB activation.
Mechanism
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.
Selectively blocks TREK-1 potassium channels (IC50: 0.12 nM). Enhances serotonin neurotransmission in dorsal raphe nucleus, triggering CREB activation and hippocampal neurogenesis.
Primary research focus with rapid effects in behavioral models within 4 days.
Research areas
- 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.
- Selectively blocks TREK-1 potassium channels (IC50: 0.12 nM). Enhances serotonin neurotransmission in dorsal raphe nucleus, triggering CREB activation and hippocampal neurogenesis.
- Primary research focus with rapid effects in behavioral models within 4 days.
- Anxiolytic properties demonstrated in preclinical anxiety models.
- Nearly doubles BrdU-positive cells after 4-day treatment.
- Promotes new synapse formation through CREB activation.
- Hippocampal and prefrontal cortex TREK-1 expression supports memory.
- Potential ischemic protection and neuronal survival support.
- 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.
Research notes
- No effects on TREK-2, TRAAK, TASK-1 channels observed
- No cardiac dysfunction or seizures in preclinical studies
- Serotonin syndrome signs
- Severe persistent headaches
- Cardiac symptoms
- Seizure activity
- Severe mood changes or suicidal ideation
- Pregnancy and breastfeeding
- Concurrent MAOI use
- 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.
FAQs
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.
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.