PE-22-28 10mg
PE-22-28 10mg
PE-22-28 is a synthetic heptapeptide (sequence: GVSWGLR) derived from the sortilin propeptide, engineered as a potent and selective antagonist of TREK-1 potassium channels. Preclinical studies demonstrate rapid antidepressant
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Vial Size
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Dose Range
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Schedule
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Primary Goal
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| 10mg vial | 50 to 200 mcg daily with conservative titration; many find 100 to 150 mcg adequate. | Daily subcutaneous injections for 12 to 16 weeks (8 weeks minimum). | Support rapid neuroplasticity, mood regulation, and neuroprotection through selective TREK-1 inhibition. |
Reconstitution Summary
Storage Summary
Reconstitution Steps
- Draw 1 mL bacteriostatic water with a sterile syringe.
- Inject slowly down the vial wall; avoid foaming.
- Gently swirl until dissolved (do not shake).
- Label and refrigerate at 2 to 8 °C, protected from light. At 10 mg/mL, 1 unit = 0.01 mL » 100 mcg on a U-100 insulin syringe.
How It Works
PE-22-28 functions as a potent and selective antagonist of TREK-1 (KCNK2) two-pore domain potassium channels. By blocking TREK-1, it depolarizes neurons and enhances excitability, leading to increased firing of serotonergic neurons and elevated monoamine neurotransmission. This mechanism produces rapid antidepressant-like effects in preclinical models: within 4 days, PE-22-28 significantly increases hippocampal neurogenesis and synaptogenesis markers, changes typically requiring weeks with conventional antidepressants. The peptide also activates CaMKII/CREB pathways that promote neuronal survival and plasticity. PE-22-28 represents a shortened, optimized analog of spadin with superior potency (IC50 ~0.12 nM versus 40 to 60 nM for spadin) and longer duration of action (~23 hours versus ~7 hours). Research also demonstrates neuroprotective effects in stroke models through biphasic dosing.
Benefits & Side Effects
- Rapid antidepressant effects: produces behavioral improvements within 4 days in rodent models;
reduces immobility in forced swim tests and decreases latency to feed in novel environments. - Enhanced neuroplasticity: increases hippocampal neurogenesis, synaptogenesis markers (PSD-95),
dendritic spine density, and BDNF expression within days. - Neuroprotection: in stroke models, preserves dopaminergic neurons, reduces motor deficits, and
prevents post-stroke depressive behavior. - Favorable safety profile: high selectivity with no effects on hERG channels (cardiac safety), no impact
on heart rate, blood pressure, glucose regulation, or pain perception in preclinical studies. No - TREK-1-related side effects or withdrawal observed.
- No human data: all evidence is from cell culture and animal studies; human safety and
pharmacokinetics remain unestablished. - Subcutaneous administration may occasionally cause minor injection-site reactions (slight redness or
tenderness).
References & Scientific Literature
- Mazella et al. Spadin, a sortilin-derived peptide targeting TREK-1 channels; novel antidepressant mechanism (PLoS Biology, 2010).
- Moha Ou Maati et al. Spadin as antidepressant; absence of TREK-1-related side effects (Neuropharmacology, 2012).
- Djillani et al. Shortened spadin analogs (PE-22-28): superior TREK-1 inhibition and antidepressant activity (Frontiers in Pharmacology, 2017).
- Pietri et al. Protective effects on stroke recovery and post-stroke depression (Neuropharmacology, 2019).