⚠ Educational reference only — not medical advice.** This article is for research and educational reference. Always consult your own physician before considering any peptide protocol. See the full Disclaimer at the end of this article.

Introduction
PE-22-28 is a synthetic short peptide derived from spadin, an endogenous propeptide produced during sortilin maturation. Investigated as a selective blocker of TREK-1 (KCNK2), a two-pore-domain potassium channel implicated in mood disorders and ischemic neuronal injury. Strictly investigational.

Mechanism of Action
Blocks the TREK-1 channel, reducing leak potassium current and producing neuronal depolarization in serotonergic neurons. Functionally similar to genetic TREK-1 knockout in mice, which displays an antidepressant-like phenotype with preserved 5-HT-system signaling. Selectivity for TREK-1 over related channels is a key feature distinguishing PE-22-28 from broader antidepressant pharmacology.

Research Indications
Preclinical: treatment-resistant depression (rodent models show antidepressant-like effects on rapid timescales), post-ischemic neuroprotection, TREK-1-associated pain syndromes.

Reconstitution
Typical 5 mg lyophilized vial: add **2.5 mL of bacteriostatic water**, swirl gently. Final concentration **2000 mcg/mL (2 mg/mL)** — each 0.05 mL (5 units on a U-100 insulin syringe) delivers 100 mcg.

Dosing Protocol (research literature)
Human dosing is not characterized. Research protocols extrapolated from preclinical work typically explore **100–500 mcg subcutaneously once daily**, or **intranasal** administration in some neuropsychiatric research designs at similar daily totals. Duration **4–8 weeks** with mood-instrument reassessment.

Administration
Subcutaneous into abdominal fat, or intranasal in CNS-endpoint research. Intranasal preparation requires compounding pharmacy involvement.

Storage & Handling
Lyophilized: refrigerate (2–8°C); freeze (–20°C) for long-term storage. Reconstituted: refrigerate; stable approximately **7–14 days**. Protect from light.

Side Effects
Human safety data are not established. Theoretical concerns: off-target effects on pain perception or seizure threshold given TREK-1’s broader physiology.

Contraindications
Pregnancy, lactation, active psychiatric crisis, seizure history. Not appropriate as a substitute for evidence-based antidepressant therapy.

Monitoring
Validated mood instruments (e.g., MADRS, HAM-D), neurological examination, adverse-event surveillance with particular attention to seizure threshold and pain perception.

Disclaimer

**This article is for informational and research-reference purposes only.** Nothing in this document constitutes medical advice, a prescription, or a recommendation from a physician. The reconstitution, dosing, and protocol information above reflects ranges commonly cited in published research and clinician-directed protocols — it is provided as reference material only, not as instructions, an endorsement of off-label use, or a substitute for individualized medical evaluation.

**Customers should do their own research and consult their own physician** before considering any peptide protocol. Whether a given compound is appropriate for an individual — and at what dose, for what duration, and alongside what monitoring — is a decision that only a licensed clinician with knowledge of that individual’s medical history, current medications, and conditions can make.