PE-22-28 (Mini-Spadin)

TREK-1 Channel Blocker | Shortened Spadin Analog

Weight: 773.89 Da
Half-life: Approximately 23 hours
Chain: 7 amino acids
3 studies
2017 latest
Emerging
Dose 50-200mcg daily
Frequency Once daily
Cycle 4-8 weeks
Storage Refrigerate at 2-8°C, use within 4-6 weeks
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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.

01 Rapid antidepressant effects within 4 days (preclinical)
02 Hippocampal neurogenesis and synaptogenesis
03 Enhanced serotonergic neurotransmission
04 Extended ~23 hour duration of action
05 300-500x greater potency than full-length Spadin

Molecular Data

Molecular Weight
773.89 Da
Chain Length
7 amino acids
Type
Linear heptapeptide
Amino Acid Sequence
One-letter: GVSWGL?
H₂N
H
G 1
O ‖ C
N
V 2
O ‖ C
N
S 3
O ‖ C
N
W 4
O ‖ C
N
H
G 5
O ‖ C
N
L 6
O ‖ C
N
H
? 7
COOH
Gly
1

Glycine

Position 1

Val
2

Valine

Position 2

Ser
3

Serine

Position 3

Trp
4

Tryptophan

Position 4

Gly
5

Glycine

Position 5

Leu
6

Leucine

Position 6

Arg
7

Arg (GVSWGLR)

Position 7

N-terminus C-terminus
Hydrophobic
Polar
Positive (+)
Negative (-)
Modified
Peak 0.0 mcg
Trough 0.0 mcg
SS Peak 0.0 mcg
SS Trough 0.0 mcg

Research Indications

Mental Health
Depression most effective

Primary research focus with rapid effects in behavioral models within 4 days.

Anxiety moderate

Anxiolytic properties demonstrated in preclinical anxiety models.

Neurogenesis
Hippocampal Neurogenesis most effective

Nearly doubles BrdU-positive cells after 4-day treatment.

Synaptogenesis effective

Promotes new synapse formation through CREB activation.

Cognition
Memory Support effective

Hippocampal and prefrontal cortex TREK-1 expression supports memory.

Neuroprotection moderate

Potential ischemic protection and neuronal survival support.

Dosing Protocols

Subcutaneous injection to abdominal fat or thigh with site rotation.

GoalDoseFrequencyRoute
Antidepressant Effect50-200mcgOnce dailySubQ
Neurogenesis Support100-200mcgOnce dailySubQ

Reconstitution Instructions

Materials Needed:
  • PE-22-28 lyophilized powder
  • Bacteriostatic water
  • Insulin syringes
  • Alcohol swabs
  1. 1 Inject BAC water slowly down vial wall
  2. 2 Gently swirl (do not shake)
  3. 3 Store refrigerated 2-8°C
  4. 4 Use within 4-6 weeks

Interactions

~
SSRIs (Fluoxetine, Sertraline)
Both enhance serotonergic pathways; monitor for excessive activity.
monitor
++
Semax/NA-Semax
Complementary neurogenesis and cognitive support.
synergistic
++
Selank
Different mechanisms for anxiety and mood support.
synergistic
++
Dihexa
Complementary neuroplasticity pathways.
synergistic
+
BPC-157
Different mechanisms, no contraindications.
compatible
!
MAOIs
Serotonin syndrome risk.
avoid

What to Expect

Days 1-4
Measurable antidepressant effects in preclinical models
Weeks 1-2
Neurogenesis and synaptogenesis processes established
Weeks 2-4
Potential mood and cognitive improvements emerge
Weeks 4-8
Sustained treatment allows full neurogenic effects

Side Effects & Safety

Common Side Effects

  • No effects on TREK-2, TRAAK, TASK-1 channels observed
  • No cardiac dysfunction or seizures in preclinical studies

Stop Signs - Discontinue if:

  • Serotonin syndrome signs
  • Severe persistent headaches
  • Cardiac symptoms
  • Seizure activity
  • Severe mood changes or suicidal ideation

Contraindications

  • Pregnancy and breastfeeding
  • Concurrent MAOI use

Quality Checklist

Good Signs

  • White to off-white lyophilized powder
  • Clear, colorless reconstituted solution
  • Certificate of Analysis with >98% purity
  • Proper cold-chain shipping

Warning Signs

  • Research compound only, not FDA-approved
  • Quality varies by supplier

Bad Signs

  • Cloudy, discolored, or particulate appearance
  • Clumped or sticky powder indicating moisture damage

References

  • Shortened Spadin Analogs Display Better TREK-1 Inhibition
    (2017)

    PE-22-28 IC50 0.12 nM vs 40-60 nM for Spadin; ~23 hour duration. Frontiers in Pharmacology.

  • Spadin: A Sortilin-Derived Peptide Targeting TREK-1 Channels
    (2010)

    Original discovery of TREK-1 blockade as antidepressant mechanism. PLOS Biology.

  • TREK-1 Deletion Results in Depression-Resistant Phenotype
    (2006)

    TREK-1 knockout mice show depression-resistant behavior in 5 tests. Nature Neuroscience.

Related Peptides

Selank synergistic

Different mechanisms for anxiety and mood support.

Dihexa synergistic

Complementary neuroplasticity pathways.

BPC-157 compatible

Different mechanisms, no contraindications.

Disclaimer

This information is for educational and research purposes only. Consult a healthcare professional before use.