Peptide Schedule
PE-22-287 residuesGVSWGLREach bubble = one amino acid. Size = residue mass. Color = chemical class.PE-22-28
Benefits
About PE-22-28
PE-22-28 is a synthetic heptapeptide (7 amino acids) derived from spadin, a naturally occurring fragment of the sortilin propeptide. It acts as a potent blocker of TREK-1 two-pore potassium channels in the brain, with an IC50 of 0.12 nM — roughly 300-fold more potent than the parent compound spadin. In animal models, PE-22-28 produces rapid antidepressant-like effects within 4 days of treatment, compared to the 3-4 weeks typical of SSRIs. It stimulates hippocampal neurogenesis, increases BDNF expression, and modulates serotonergic signaling. PE-22-28 also shows improved in vivo stability over spadin, with a functional duration of approximately 23 hours versus 7 hours. Preclinical stroke research has demonstrated neuroprotective effects, including reduced infarction size and improved motor and cognitive recovery. All current evidence comes from rodent studies — there are no published human clinical trials. This peptide remains strictly a research tool and should be approached with appropriate caution given the absence of human safety data.
Who Should Consider PE-22-28
- Researchers studying TREK-1 potassium channel pharmacology
- Individuals exploring preclinical nootropic and mood-support compounds
- Adults interested in neurogenesis-promoting peptides (with medical supervision)
- Those researching alternatives to conventional antidepressant mechanisms
How PE-22-28 Works
PE-22-28 selectively blocks TREK-1 (TWIK-related potassium channel 1), a two-pore domain potassium channel expressed throughout the brain. TREK-1 normally hyperpolarizes neurons and dampens excitability. By inhibiting TREK-1, PE-22-28 increases neuronal excitability in mood-regulating circuits, enhances serotonergic and dopaminergic transmission, and triggers downstream BDNF signaling. This cascade promotes hippocampal neurogenesis and synaptogenesis. Unlike spadin, PE-22-28 does not appear to inhibit other K2P family channels (TREK-2, TRAAK, TASK, TRESK), suggesting high target specificity.
What to Expect
Based on animal data, initial mood and cognitive effects may begin. TREK-1 blockade and downstream serotonin modulation start rapidly. Individual responses in humans are undocumented.
In rodent models, measurable antidepressant effects and early neurogenesis are observed by day 4. Anecdotal reports suggest improved mood stability and mental clarity.
Continued hippocampal neurogenesis and BDNF elevation expected based on preclinical data. End of standard 4-week cycle.
Neurogenesis-driven benefits may persist beyond the active dosing period. Allow a washout period equal to the on-cycle length before resuming. Long-term effects in humans are unknown.
Dosing Protocol
| Level | Dose / Injection | Frequency |
|---|---|---|
| Beginner | 100mcg | Daily |
| Moderate | 200mcg | Daily |
| Aggressive | 400mcg | Daily |
Note: Shortened spadin analog. TREK-1 potassium channel blocker (IC50 0.12 nM). Derived from sortilin propeptide. Animal research only — no human trials. Intranasal preferred for CNS access.
How to Inject PE-22-28
Intranasal delivery is preferred for direct CNS access. Reconstitute lyophilized powder with bacteriostatic water. For subcutaneous injection, rotate injection sites (abdomen, thigh). Administer in the morning on an empty stomach. All dosing information is derived from animal research and community anecdotal reports — no human dosing guidelines have been clinically established.
Cycling Protocol
Cycling recommendations are extrapolated from community protocols — no human clinical data supports a specific schedule. The 4-on/4-off pattern is commonly used to prevent potential receptor desensitization.
Pharmacokinetics
Source: Functional duration ~23h in mice (vs. ~7h for spadin); Djillani et al. 2017, PMID 28955242. No human PK data available.
Loading the interactive decay curve.
Side Effects
No human safety data exists. In rodent studies, PE-22-28 was generally well-tolerated with no reported significant adverse effects. However, the absence of human trials means the full side-effect profile is unknown. Potential concerns include off-target ion channel effects and unknown long-term consequences of TREK-1 inhibition.
Contraindications
- Pregnancy or breastfeeding — no safety data
- Known hypersensitivity to spadin-derived peptides
- History of seizure disorders — TREK-1 blockade increases neuronal excitability
- Cardiac arrhythmias or conduction disorders — K+ channel modulation warrants caution
- Children and adolescents — no safety or efficacy data
Drug Interactions
- SSRIs and SNRIs — PE-22-28 modulates serotonin pathways; combining may increase serotonergic tone
- MAO inhibitors — theoretical risk of excessive monoamine activity when combined with TREK-1 blockade
- Antiepileptic drugs — TREK-1 inhibition increases neuronal excitability, potentially counteracting anticonvulsant mechanisms
- Potassium channel openers (e.g., minoxidil, diazoxide) — pharmacological antagonism at the channel level
- QT-prolonging medications — theoretical concern given K+ channel involvement; ECG monitoring advised
Storage & Stability
Molecular Profile
Related Peptides
References
- Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant ActivityPubMed 28955242
- Spadin, a sortilin-derived peptide, targeting rodent TREK-1 channels: a new concept in the antidepressant drug designPubMed 20405001
- First evidence of protective effects on stroke recovery and post-stroke depression induced by sortilin-derived peptidesPubMed 31325429
- Fighting against depression with TREK-1 blockers: Past and future — a focus on spadinReview
- Spadin as a new antidepressant: absence of TREK-1-related side effectsPubMed 21807005