PE-22-28 — Clinical Reference

**⚠ 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. The platform and the author make no claim that any compound described here is safe, effective, or appropriate for any particular person or purpose, and accept no responsibility for outcomes arising from self-directed use of the information.