Important limitations
- Individual claims and source links have not yet completed editorial verification.
- Evidence level, applicable study model, formulation, route and population remain unassigned.
PE-22-28
PE-22-28 is a seven-amino-acid fragment (Gly-Val-Ser-Trp-Gly-Leu-Arg) of the propeptide released when the receptor sortilin matures, designed in 2017 by Jean Mazella, Marc Borsotto.
Dosing & scaling, explained
The moderated mass amounts below are retained for comparison. Near-duplicates, mix-dependent volumes and device markings are excluded. This is educational source context, not a protocol or recommendation.
Mass amounts available for comparison
- Lower range200 mcgDosing
Recorded example with no verified study backing; shown for amount literacy only.
- Mid range600 mcgDosing
Recorded example with no verified study backing; shown for amount literacy only.
Only mcg or mg amounts are retained. The calculator derives mL, syringe units or pen clicks from the current vial strength, water volume and device.
No independently verified schedule
Evidence context
No clinical amount or schedule is inferred from this material. Source verification is pending, and every displayed amount remains educational context rather than guidance.
Storage, handling and interpretation
Product identity
Verify the exact compound, formulation and amount against the product label or certificate before calculation.
Storage & handling
Follow the product label, certificate and validated laboratory SOP; no universal storage assumption is applied here.
Prepared solutions
Label concentration and preparation date, use sterile technique where applicable, and follow a validated stability protocol.
Reported protocols for PE-22-28
What published studies and recent community write-ups report about amounts, timing and course length. 2 preclinical and 3 community-reported rows, each linked to its source. These are descriptions of what others report, not instructions, and nothing here is medical advice.
| Context | Dose | Frequency | Route | Course | Source |
|---|---|---|---|---|---|
| Preclinical2 rows | |||||
| Preclinical: antidepressant-like effects and neurogenesis in miceAdult mice, including a 7-week corticosterone model of depression (10 animals per group) | 3.0-4.0 mcg/kg per injection; 1 mg/kg by gavage in the oral arm | Single dose 30 minutes before testing, or once daily for 4 days | Intraperitoneal injection; oral gavage | Acute, or a 4-day sub-chronic courseNot applicable | Frontiers in Pharmacology (PubMed Central)2017 |
| Acute 3.0-4.0 mcg/kg cut forced-swim immobility from about 162 to 92 seconds, and a 4-day course at 3.0 mcg/kg shortened learned-helplessness escape latencies, reduced latency to feed in the novelty-suppressed feeding test and roughly doubled BrdU-labelled new hippocampal cells. Spadin needed 100 mcg/kg for comparable effects, and the authors note that the modified analog G/A-PE 22-28 kept its forced-swim effect for about 23 hours after one 32 mcg/kg dose despite a short in vitro serum half-life. | |||||
| Preclinical: stroke recovery and post-stroke depression in miceMice with focal cerebral ischemia (middle cerebral artery occlusion), compared with spadin and escitalopram arms | 0.03 mcg/kg for the first 7 days, then 3 mcg/kg | Once daily for 7 days after ischemia, then once daily on 4 days per week | Intraperitoneal injection in 100 microlitres of saline, first dose 30 minutes after the onset of ischemia | 7 days of low-dose treatment followed by weeks of high-dose treatment until sacrifice3 days off per week during the high-dose phase | Neuropharmacology (PubMed)2019 |
| The authors report a biphasic action: at the 100-fold lower dose the peptide increased TREK-1 activity and protected against weight loss, nigral dopaminergic degeneration and motor and cognitive deficits, while the higher dose blocked the channel and prevented depression-like behaviour in the forced swim and novelty-suppressed feeding tests. Escitalopram at 1 mg/kg served as the comparator, and all findings come from the laboratory that owns the patents on these peptides. | |||||
| Community-reported3 rows | |||||
| Community protocol, intranasal and subcutaneous | 200-400 mcg intranasally, or 100-200 mcg subcutaneously; total kept under 600 mcg | Once daily, in the morning | Intranasal from a metered sprayer, or subcutaneous (10 mg vial in 2 mL gives 5 mg/mL, so 200 mcg is 4 units) | 4-8 weeksA break after each run, length not fixed | Community resource2026 |
| This September 2026 guide states that every figure is community-derived for a compound dosed only in mice, that the 4-8 week pattern mirrors research-peptide habit rather than anything compound-specific (the mouse work lasted 4 days), and that lethargy at higher doses is the reason for the morning timing and the 600 mcg ceiling. It also notes that no human data quantify nasal absorption. | |||||
| Tiered intranasal ladder with cycle options | 100-200 mcg (beginner), 200-300 mcg (intermediate) or 300-500 mcg (advanced) per administration; 100-300 mcg subcutaneously as an alternative | Once daily in the morning, or twice daily (morning and early afternoon) at the intermediate and advanced tiers | Intranasal spray (about 0.1 mL per actuation); subcutaneous | 4 weeks (conservative), 6 weeks (standard) or 8 weeks (extended); a 5-days-on, 2-days-off weekly pattern also described2-4 weeks off after 4 weeks, 3-4 weeks off after 6 weeks, 4 weeks off after 8 weeks | Community resource2026 |
| This August 2026 guide is explicit that its ranges describe community practice, that nothing published supports a benefit above 500 mcg per day and that every study used injected dosing in rodents. It recommends 1-2 weeks at the lowest tier before any increase. | |||||
| Aggregated forum protocols | 200-400 mcg intranasal (standard); 100-200 mcg subcutaneous (low-dose); 100 mcg rising to 150-200 mcg (titration) | Once daily, morning | Intranasal or subcutaneous | 4-8 weeks; 8-16 weeks for the slow titration variantNot specified | Community resource2026 |
| Compiled from about 40 forum and vendor reports in February 2026, this page records mood elevation within days as the most common claim and lethargy above 500-600 mcg as the most common complaint, while stressing that no safety or toxicology study exists. Its statement that the mouse work used 0.1 mg/kg does not match the primary paper, which used 3-4 mcg/kg for PE 22-28 and 100 mcg/kg for spadin. | |||||
How a course is commonly described
- Weeks 1-2Community-reported
Community guides start at 100-200 mcg intranasally once each morning (or 100 mcg subcutaneously) and hold there for 1-2 weeks to check for sedation. Forum reports describe mood changes within days, which is also when nasal irritation or lethargy would show up.
- Weeks 3-6Community-reported
The dose settles at 200-400 mcg intranasally or 150-200 mcg subcutaneously, morning only, with a self-imposed ceiling of 600 mcg a day because higher amounts are reported to cause lethargy. Six weeks is described as the longest course with any community track record.
- BreakCommunity-reported
Runs end at 4-8 weeks followed by 2-4 weeks off, or a 5-days-on, 2-days-off week is used instead to interrupt continuous channel blockade. No source offers evidence for either pattern.
- Preclinical comparisonPreclinical
The mouse studies gave 3-4 mcg/kg by intraperitoneal injection for 4 days, or a stroke regimen of 0.03 mcg/kg daily for a week followed by 3 mcg/kg four days a week; nothing longer than a few weeks has been studied in any animal, and no study has used the nasal route.
- PE-22-28 has never been given to a human in any published study or registered trial. The intranasal and subcutaneous microgram doses above are forum conventions; the only tested routes are intraperitoneal injection and oral gavage in mice.
- The mouse data show a biphasic effect on TREK-1 (activation at 0.03 mcg/kg, blockade around 3 mcg/kg), so dose scaling is not straightforward, and the long duration of action (about 23 hours) was measured for a modified analog rather than for PE 22-28 itself.
- TREK-1 channels are also present in heart and pain pathways; the developers report no cardiac or pain-threshold effects at effective doses, but that claim has not been tested outside their laboratory and no toxicology study exists.
Sources for this section (5)
- Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity
- First evidence of protective effects on stroke recovery and post-stroke depression induced by sortilin-derived peptides
Plus 3 community resources (dosing guides, forum threads and vendor write-ups), reported above but not linked.
Overview
PE-22-28 is a seven-amino-acid fragment (Gly-Val-Ser-Trp-Gly-Leu-Arg) of the propeptide released when the receptor sortilin matures, designed in 2017 by Jean Mazella, Marc Borsotto and colleagues at the CNRS Institute of Molecular and Cellular Pharmacology in Nice from the breakdown products of their earlier 17-residue peptide spadin. It blocks the TREK-1 background potassium channel with an IC50 of 0.12 nM, several hundred times more potently than spadin, and in mice it reduced depression-like behaviour, increased hippocampal neurogenesis within 4 days and kept working for roughly 23 hours after a single injection; the same group later reported that very low doses protected mice after experimental stroke while higher doses prevented post-stroke depression. All published work is in mice and cultured cells using intraperitoneal injection or oral gavage; there is no human study, no registered trial and no approval, and the intranasal spray favoured by the research-peptide community has never been tested in any species.
What researchers are exploring
These themes organize the educational information currently available. Individual claims remain under source review and are not treatment claims.
- 1
Research on PE-22-28
Understanding TREK-1 and therapeutic applications
What is known and what still needs verification
Available context is organized without assigning unsupported study models or evidence grades.
- Not graded
Research on PE-22-28
Understanding TREK-1 and therapeutic applications
Amounts recorded for PE-22-28
These amount records are independent from vial strength, reconstitution volume and measuring device. A recorded source is not the same as study backing, and these values are not recommendations.
- 1Dosing · lower endpointSign in for schedule, duration and source context.200 mcg
- 2Dosing · upper endpointSign in for schedule, duration and source context.600 mcg
Chemistry identifiers
Sequence, synonyms and registry identifiers as recorded in PubChem, the National Library of Medicine's open chemistry database. Formula, mass and CAS number are summarized at the top of the page.
Sequence
Gly-Val-Ser-Trp-Gly-Leu-Arg
Also listed as
PE 22-28, Mini-spadin, Spadin analog (shortened), GVSWGLR, L-Arginine, glycyl-L-valyl-L-seryl-L-tryptophylglycyl-L-leucyl- (PubChem record title), PE 22-28 (acetate), HY-P3581, CS-0615995
InChIKey
CMNBQRXBBJQIOA-YIHYGEMESA-N
IUPAC name
(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-aminoacetyl)amino]-3-methylbutanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]acetyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid
Limitations and unknowns
Sources
1 link carried over from the earlier page, awaiting verification.