PE-22-28: what the studies show, status and safety
Summary
PE-22-28 is a lab-made peptide of seven building blocks, sold online as a research chemical. Almost everything known comes from one paper published in 2017 by one French research group, which reported that mice floated less in a swim test. Nobody has taken it in a study, no toxicity data exist, and the one independent check came out largely negative.
Key findings at a glance
- One paper carries almost the whole case. The 2017 study that first described PE-22-28 is still the only work that characterises the peptide itself [1]. A search of PubMed on 7 September 2026 for the peptide by name returned exactly one hit [2].
- Not one registered study in people. Queries to the ClinicalTrials.gov registry on 7 September 2026 for PE-22-28 and for its parent molecule spadin each returned zero studies [3].
- It blocked a potassium channel at 0.12 nM in cells. In one cell line, PE-22-28 shut down the TREK-1 channel at a concentration more than 300 times lower than spadin needed, which was 40 to 60 nM [1].
- Mice stayed passive for 91.8 seconds instead of 161.7. In the forced swim test, a single injection cut the time mice spent floating still, with 10 animals per group (p below 0.0001) [1].
- The independent check of the idea came out negative. A group outside the original laboratory found in 2020 that spadin did not block the channel under normal conditions. It only disturbed one particular way of switching the channel on [4].
- The effect reverses with dose. In a mouse stroke model, 0.03 µg/kg opened the channel while 3 µg/kg closed it, a hundredfold gap between two opposite actions [5].
- No toxicity study exists, in any species. Not a single acute, repeat-dose, genetic, reproductive or cancer study has been published [2].
- Banned in sport around the clock. Class S0 of the 2026 Prohibited List catches PE-22-28 through its wording rather than by naming it [6].
What it is
PE-22-28 is a synthetic peptide of seven building blocks, Gly-Val-Ser-Trp-Gly-Leu-Arg [7]. Its name is purely descriptive: PE stands for propeptide, and 22-28 are the positions it occupies in that longer chain. The propeptide itself is 44 building blocks long and is snipped off inside the cell while a protein called sortilin is being made [8].
No pharmaceutical company developed it. The whole story runs through one academic group at the Institute of Molecular and Cellular Pharmacology in Valbonne, southern France. The institute belongs to the national research agency CNRS [1].
In 2010 that group described a 17-building-block piece of the same propeptide, named spadin [9]. Spadin broke down quickly in blood, so they studied the fragments it left behind. Shortening the molecule step by step brought them to PE-22-28 in 2017 [1].
Quick facts
| Field | Value | Ref |
|---|---|---|
| Common name | PE 22-28, also written PE-22-28 and mini-spadin | [1], [10] |
| Class | Lab-made peptide of seven building blocks, cut from a peptide the body makes itself | [1], [8] |
| Sequence | Gly-Val-Ser-Trp-Gly-Leu-Arg | [7], [8] |
| Formula and mass | C35H55N11O9, 773.9 g/mol | [7] |
| Parent molecule | Spadin, 17 building blocks, about 1849 g/mol | [8], [9] |
| How long it lasts in the body | Never measured, in any species | [2] |
| Status | Research chemical, approved nowhere | [2] |
| Developer | None; an academic group at CNRS in Valbonne, France | [1] |
| Patent | EP3526244B1, granted 6 September 2023, expected to run to 2037 | [11] |
| CAS registry number | 1801959-12-5, from database entries rather than an official check | [7] |
| PubChem CID | 165437303 | [7] |
| InChIKey | CMNBQRXBBJQIOA-YIHYGEMESA-N | [7] |
| Official identifiers and drug names | None assigned | [2] |
The peptides used in the published experiments were bought from a commercial synthesis company in Luxembourg. Every result therefore rests on manufactured material rather than anything extracted from tissue [1]. Nothing has been published about how stable PE-22-28 itself is in solution.
How it works
Nobody has measured what PE-22-28 does in a person. Everything below comes from cells in dishes, frog eggs used as test systems, and mice, and all of it is proposed rather than established.
- Closing a potassium channel called TREK-1. This is the central claim. In a human cell line grown to carry the channel, PE-22-28 blocked it at 0.12 nM, against 40 to 60 nM for spadin in the same setup [1]. TREK-1 sits in nerve cell membranes and lets potassium leak out, which makes those cells harder to excite.
- Only when the channel is already open. The channels in those experiments had first been opened with 10 µM arachidonic acid, so the authors argue the peptide needs an open channel to act on [1].
- Apparently only that one channel. At 100 nM, the peptide left four related potassium channels unchanged, and at 10 µM it did not touch the hERG channel of the heart either [1].
- New nerve cells and new connections downstream. After four days of treatment, mouse brains showed more newly made cells in the hippocampus, counted in five animals per group, and cultured nerve cells made more of a protein found at connection points [1]. The largest rise in new cells came from a chemically modified version rather than from PE-22-28 itself [1].
- A serotonin link, inherited from spadin. For spadin, the group reported faster firing of serotonin-producing neurons and more of the growth factor BDNF in the hippocampus [9], [12]. Whether the same holds for PE-22-28 has not been tested to the same depth.
- Opposite actions at different doses. In the stroke study, low doses opened the channel and higher ones closed it, and the authors used the two ends deliberately for two different purposes [5].
- Something in the pancreas as well. Related work reports that blocking TREK-1 depolarises insulin-producing cells, raises calcium inside them and protects them from being killed by an inflammatory signal [13], [14].
TREK-1 is a plausible target rather than a proven one. The channel earned its reputation in 2006, when mice bred without the gene turned out to be resistant to depression-like behaviour [15]. That was a genetic deletion, not a drug.
What the studies found
Every result on this page comes from a mouse, a rat, a frog egg or a dish of cells. No study of any kind has given PE-22-28 to a person.
Counts as of 7 September 2026. The single PubMed hit is the 2017 paper that describes the peptide; the five Europe PMC hits use the name mini-spadin. Sources [1], [2], [3].
Behaviour in mice
Animal data In the forced swim test, mice given a single injection of 3.0 to 4.0 µg/kg spent 91.8 ± 6.1 seconds floating passively. Mice given salt water spent 161.7 ± 6.5 seconds, with 10 animals per group (p below 0.0001) [1]. The test measures how long an animal stops struggling. It is a screening tool for spotting molecules worth pursuing, and it does not measure mood.
Animal data Mice were made anxious and passive by seven weeks of the stress hormone corticosterone. PE-22-28 at 3.0 µg/kg brought the same measure to 98.1 ± 8.8 seconds and spadin at 100 µg/kg to 117.4 ± 6.9 seconds. Untreated animals reached 164.9 ± 6.0 seconds, and both treated groups differed from them at p below 0.0001 [1].
Forced swim test after seven weeks of corticosterone, injection into the abdomen, 10 mice per group, both treated groups p below 0.0001 against control. Source [1].
Animal data A third test puts food in an open, unfamiliar cage that mice are wary of entering. Four days of 3 µg/kg shortened the delay before they ate (p below 0.05) [1]. Standard antidepressants usually need weeks to shift this measure, which is why the authors read it as a sign of faster onset. The same four days also shortened escape times in a learned helplessness test (p below 0.05) [1].
How long the effect lasted
Animal data After a single injection, the swim test effect faded with a half-life of 14 to 23 hours, depending on compound and dose. Spadin at 100 µg/kg managed 6 hours [1]. These numbers come from two chemically modified versions of PE-22-28, not from the peptide sold under that name.
Stroke
Animal data One study, published in 2019 under the name mini-spadin, is the only work that looks beyond depression-like behaviour [5]. Mice had an artery blocked to cause a stroke. A low dose of 0.03 µg/kg began 30 minutes later and continued daily for seven days. It was followed by less weight loss, less late loss of dopamine-making nerve cells in the substantia nigra, a region that governs movement, and better movement and memory.
Animal data A higher dose of 3 µg/kg, given on four days a week afterwards, was followed by less depression-like behaviour. The full text sits behind a paywall, so these figures come from the abstract [5].
The pancreas
Animal data Work from the same laboratory reports that spadin lowered the resting voltage across insulin-producing cells by about 12 mV. It also raised calcium inside those cells and increased insulin release in mice [13]. A later paper reports that the propeptide, spadin and PE-22-28 all protected such cells from being killed by an inflammatory signal, and that PE-22-28 also made them multiply [14]. For a molecule aimed at the brain, an effect on blood sugar control is an unwanted one.
Findings that point the other way
In vitro The most important contrary result came from a group with no connection to the original laboratory. Working in frog eggs in 2020, they found that spadin did not block TREK-1 or its relative TREK-2 under normal conditions, while barium blocked both [4]. It also failed to block channels that had been switched on chemically or by a mutation.
In vitro All it did was disturb the subsequent switching-on by arachidonic acid, and only for TREK-1. The authors concluded there was no activity of its own. This work tested spadin, and nobody outside the original group has repeated the PE-22-28 experiments [2].
The three human papers, and what they are not
Observational Three published studies did involve people, and they are regularly misread. All three measured blood levels of the body's own propeptide as a possible marker. Levels were lower in people with major depression than in healthy controls (p = 0.035) [16]. In 45 people with treatment-resistant depression, levels rose about a month after electroconvulsive therapy (p = 0.005), and only in those who responded [17].
Observational In 204 people followed for up to 60 months after a stroke, levels tracked depression scores (p = 0.006) but not anxiety scores (p = 0.75) [18]. Nobody in any of these studies was given PE-22-28 or spadin.
The target, tested by others
Animal data Two independent groups have tested TREK-1 itself rather than this peptide. In stressed rats, channel blockers reversed depression-like behaviour at least a week sooner than fluoxetine did [19]. In stressed mice, switching the channel off in hippocampal nerve cells eased the same behaviour and preserved connection proteins [20]. Both support the target. Neither used PE-22-28.
What is still unknown
- Whether anything seen in mice happens in a person. There are no human data by any route [3].
- Whether the peptide is safe. No toxicity study exists, in any species, of any kind [2].
- How the body takes it up, breaks it down and gets rid of it. Nothing has been published [2].
- Whether it reaches the brain through the nose. That route has never been tested [2].
- Whether the central claim holds outside the laboratory that made it. No independent group has repeated the work [2], [4].
Side effects and safety
There is no list of side effects, because there is no documented use in people. Nothing has been reported, which is not the same as nothing happening.
- No safety testing whatsoever. Nothing on single doses, repeated doses, genetic damage, fertility, offspring or cancer risk has been published for PE-22-28, in any species [2].
- No authority has ever looked at it. Two FDA pages listing raw substances used in pharmacy compounding were searched in full on 7 September 2026 and returned nothing [21], [22]. The same pages name BPC-157, KPV and ipamorelin, so the absence is real. It means the substance was never put forward, not that it was cleared.
- One reassuring cell result, from the developers themselves. At 10 µM the peptide left the hERG heart channel unchanged, which is the standard first check for a dangerous heart rhythm effect [1]. It is a single in vitro measurement from the group that made the molecule.
- A pain signal from independent work. Blocking TREK-1 with spadin increased pain behaviour and heightened sensitivity in rats, while an opener of the channel reduced it [23]. This contradicts the original group's report that spadin left pain untouched [24].
- An effect on blood sugar nobody followed up. Blocking the channel raised insulin release in mice [13]. No safety study has tracked that consequence.
- More is not stronger, and can be opposite. Because the response in mice reverses between 0.03 and 3 µg/kg, a higher amount does not simply mean a weaker or stronger version of the same effect [5].
- Spadin's safety record does not transfer. A 2012 screen reported that spadin left pain, seizures and heart function alone [24]. PE-22-28 blocks the channel more than 300 times more strongly, so it is a different pharmacological proposition [1].
Two further gaps deserve naming. Nothing is known about whether the peptide provokes an immune response, a standard question for any peptide. And nothing is known about the purity of what is actually sold, because no independent analysis of commercial material exists [2].
Doses used in studies
These are the doses used in the cited studies, listed for reference. They are not a recommendation.
Every line below describes a mouse, a rat or a dish of cells. The amounts are millionths of a gram per kilogram of animal. They were delivered by injection or by a tube into the stomach. None of them has any counterpart in a person.
| Study | Model | Dose | Route | Duration | Ref |
|---|---|---|---|---|---|
| Djillani 2017, swim test, single dose | Mouse, naive | 3.0–4.0 µg/kg | Injected into the abdomen | Once, measured after 30 minutes | [1] |
| Djillani 2017, comparison arm | Mouse, naive | 100 µg/kg spadin | Injected into the abdomen | Once | [1] |
| Djillani 2017, repeated treatment | Mouse | 3.0 µg/kg | Injected into the abdomen | Once daily for 4 days | [1] |
| Djillani 2017, given by mouth | Mouse | 1.0 mg/kg | Tube into the stomach | Once daily for 4 days | [1] |
| Djillani 2017, stress hormone model | Mouse, after 7 weeks of corticosterone | 3.0 µg/kg, against 100 µg/kg spadin | Injected into the abdomen | Once, or daily for 4 days | [1] |
| Djillani 2017, new nerve cells | Mouse, marked with BrdU | 3.0–4.0 µg/kg per day | Injected into the abdomen | 4 days | [1] |
| Djillani 2017, duration of effect | Mouse, 10 per time point | 3.2 or 32 µg/kg of a modified version | Injected into the abdomen | Once, followed for 24 hours | [1] |
| Djillani 2017, channel measurements | Human cell line carrying TREK-1 | 100 nM for selectivity, 10 µM for the heart channel | Added to the bath | Single measurement | [1] |
| Pietri 2019, protection after stroke | Mouse, blocked artery | 0.03 µg/kg | Injected into the abdomen | Daily for 7 days, from 30 minutes after the stroke | [5] |
| Pietri 2019, behaviour after stroke | Mouse, after stroke | 3 µg/kg | Injected into the abdomen | Four days a week thereafter | [5] |
| Mazella 2010, spadin reference values | Mouse | 10⁻⁶ M into a vein or 10⁻⁵ M into the abdomen, each as a 100 µl bolus | Into a vein or the abdomen | Daily for 4 days, or for 15 days | [9] |
Development and approval status
From a laboratory idea to a product nobody assessed
- 2006Mice without the TREK-1 gene resist depression-like behaviourThe finding that made the channel a target, ref [15]
- 2010Spadin described, the 17-building-block parentSame laboratory in Valbonne, ref [9]
- 2017PE-22-28 published, the seven-building-block versionStill the only paper characterising it, ref [1]
- 2019Stroke study, published under the name mini-spadinThe only work beyond depression-like behaviour, ref [5]
- 2020Independent check of the mechanism comes out largely negativeFrog eggs, tested spadin, ref [4]
- 6 September 2023European patent granted to the research agencyEP3526244B1, expected to run to 2037, ref [11]
- 7 September 2026Registry and authority searches return nothingNo trial, no listing, no assessment, refs [3], [21], [22]
- 2006 — mice bred without the channel turn out resistant to depression-like behaviour, which establishes the target [15].
- 2010 — spadin is described, and the field of TREK-1 blockers as antidepressants begins [9].
- 2017 — PE-22-28 is derived from spadin's breakdown fragments and published [1].
- 2019 — the stroke study appears, under the alternative name [5].
- 2020 — an outside group fails to reproduce the mechanism for spadin [4].
- 2023 — the European patent is granted to CNRS and the university in Nice [11].
- 2026 — no registered trial, no listing, no authority assessment [3], [21], [22].
| Market | Status | Note | Ref |
|---|---|---|---|
| United States | Not approved | On no compounding list, never assessed | [21], [22] |
| European Union | Not approved | No drug name and no classification code | [2] |
| Germany | Not approved | No special provision | [2] |
| United Kingdom | Not approved | Not separately checked | [2] |
| Australia | Not classified | Not separately checked | [2] |
| Canada | Not approved | Not separately checked | [2] |
| Switzerland | Not approved | Not separately checked | [2] |
| Japan | Not approved | A patent exists, which is not an approval | [11] |
Where the table says not separately checked, no search of that particular national register was run. The entry rests instead on the absence of any drug name, classification code or official identifier anywhere in the world [2].
What is actually sold is a different thing again. Ready-mixed nasal sprays are widely offered online, advertised with phrases such as antidepressant-like effects and rapid-acting mood modulation [25]. Combination sprays with Selank are sold as well, and no experiment of any kind has examined that mixture.
The nasal route appears in no animal study and in no patent. The one formulation patent covering the peptide, since abandoned, claims application to the skin and never mentions the nose [26].
Anti-doping
PE-22-28 is banned in sport at all times, both in and out of competition. It is not printed on the 2026 Prohibited List by name; it falls under class S0, which covers "any pharmacological substance which is not addressed by any of the subsequent sections of the List and with no current approval by any governmental regulatory health authority for human therapeutic use" [6]. The same wording names drugs under pre-clinical development as an example, which is exactly what this is.
The list of the American college sports association does not name it either, but its class for peptide hormones and analogues catches it, and the association states that its list is neither complete nor final [27]. No test method for the peptide has been published, which changes nothing about the ban. Further detail sits under peptides banned in sport.
Compared with related peptides
| Peptide | What it acts on | Human studies | Status |
|---|---|---|---|
| PE-22-28 | TREK-1 potassium channel, blocked at 0.12 nM in one cell line [1] | None at all [2], [3] | Approved nowhere [2] |
| Spadin | The same channel, at 40 to 60 nM in the same experiment [1] | None registered [3] | Approved nowhere, patented [11] |
| Selank | Not established; a copy of a natural immune peptide [28] | Russian trials behind the approval [28] | Over-the-counter medicine in Russia, approved nowhere else [28] |
| Semax | Not established; a copy of a piece of the hormone ACTH [29] | Russian trials behind the approval [29] | Prescription medicine in Russia, approved nowhere else [29] |
Spadin is the only close relative in the strict sense, since PE-22-28 is literally its last seven building blocks. The gap between them matters. PE-22-28 blocked the channel more than 300 times more strongly in the same experiment [1]. Everything reported about spadin's serotonin effects, its safety screen and its behaviour over three weeks was measured on spadin [9], [24].
Selank and Semax are often sold alongside PE-22-28 as nasal sprays, and sometimes mixed with it in a single bottle. The resemblance ends at the delivery form. Both are approved medicines in Russia with trial data behind them, however contested that data may be elsewhere [28], [29]. PE-22-28 has never been given to anyone in a study, and no experiment has examined any combination of these peptides.
Common misconceptions
- "PE-22-28 and spadin are the same thing." They are two molecules from one laboratory. Spadin has 17 building blocks and about 1849 g/mol, PE-22-28 the last seven and 773.9 g/mol [7], [8]. Most of what is written about spadin was never tested on PE-22-28 [1], [9].
- "Mini-spadin is something else again." It is the same molecule under a second name given by the same group [10]. The 2019 stroke study is filed under that name only, which is why searches for one name miss the other [5].
- "It is a fast-acting antidepressant." That claim rests on mice floating less in a water tank and eating sooner in a strange cage, after four days [1]. Neither test measures mood, many molecules that passed them failed later in people, and for this one no trial has ever been run [3].
- "There are human studies, so there is human evidence." The three human papers measured the body's own propeptide in blood as a marker of depression [16], [17], [18]. Nobody received the peptide. They are observations of a marker, not treatments.
- "The nasal spray is the studied form." No published experiment and no patent used the nose [1], [5], [26]. Uptake, absorption and tolerance by the nose lining are entirely unstudied.
- "It is sold for collagen and wound healing, so it must do that." Not one publication examines PE-22-28 in skin, collagen or wound repair [2]. That description appears in product listings and looks like a mix-up with unrelated skin peptides.
- "Blocking TREK-1 is an established principle like blocking serotonin reuptake." No medicine approved anywhere works this way on purpose. Fluoxetine happens to block the same channel, and a metabolite of ketamine was reported to act there too [30], [31]. The target is plausible without being validated for any particular peptide.
- "The PubChem entry for spadin gives its true mass." That record has 18 building blocks and 2012.3 g/mol, because it describes a laboratory version with an extra tyrosine added for radioactive labelling [32]. The molecule used in the studies weighs about 1849 g/mol [8], [9].
Frequently asked questions
Has PE-22-28 ever been tested in humans?
No. A search of the ClinicalTrials.gov registry on 7 September 2026 returned no study of PE-22-28 and none of its parent molecule spadin. No case report and no informal series has been published either, despite the peptide being sold openly as a nasal spray.
Is PE-22-28 approved anywhere?
No country has approved it. There is no international drug name, no drug classification code and no entry in any national medicines register. The peptide never entered an approval process at all, so no authority has ever assessed it.
Is PE-22-28 the same thing as spadin?
No, they are two different molecules from the same laboratory. Spadin has 17 building blocks, PE-22-28 has the last seven of them. Most of the published work usually described as spadin research was done on spadin, not on PE-22-28.
Why is PE-22-28 also called mini-spadin?
The research group that made it uses both names for the same molecule. The 2019 stroke study is published under mini-spadin, and its title and abstract never mention PE-22-28. That is why searches for one name miss the work done under the other.
Is PE-22-28 a fast-acting antidepressant?
That description comes from mice, not from people. Researchers measured how long mice stayed passive in a water tank and how quickly they approached food in an unfamiliar cage after four days of injections. Neither test measures mood, and no trial in people has ever been run.
What are the side effects of PE-22-28?
Nobody knows, because nobody has documented anyone taking it. There is no toxicity study in any species, no data on how the body handles the peptide, and no assessment by any medicines authority. Silence in the records is not a safety finding.
Does the PE-22-28 nasal spray work the way the studies did?
The nasal route appears in no animal experiment and in no patent covering the peptide. The published work used injection into the abdomen or a vein, and in one case a tube into the stomach. Nothing is known about nasal uptake or how the nose lining tolerates it.
Are there human studies on the propeptide that PE-22-28 comes from?
Yes, but they are measurement studies, not treatment studies. Three papers measured blood levels of the body's own propeptide in people with depression or after a stroke. No participant in any of them received PE-22-28 or spadin.
Why does this page list PE-22-28 doses?
The doses are facts reported in published mouse and cell experiments, listed so the evidence can be read as it stands. They are measured in millionths of a gram per kilogram of mouse and cannot be converted to a person.
Is PE-22-28 banned in sport?
Yes, at all times, in and out of competition. Class S0 of the 2026 Prohibited List covers any drug-like substance that no health authority currently approves for use in people. PE-22-28 is caught by that wording rather than printed on the list by name.
Sources
- Djillani A, Pietri M, Moreno S, Heurteaux C, Mazella J, Borsotto M (2017). Shortened spadin analogs display better TREK-1 inhibition, in vivo stability and antidepressant activity. Frontiers in Pharmacology 8:643. PMID 28955242. DOI 10.3389/fphar.2017.00643. Full text read via PMC5601071 on 7 September 2026.
- Literature and register review by myPeptides, 7 September 2026. PubMed searched under six strategies, of which "PE-22-28 peptide" returned one hit and "spadin" 80; Europe PMC searched for "mini-spadin", returning five hits, all preclinical or reviews. No toxicity study, no pharmacokinetic study, no human case report, no independent replication and no official identifier was found. https://pubmed.ncbi.nlm.nih.gov/
- ClinicalTrials.gov API v2. Queries for "PE-22-28", "spadin" and "TREK-1" run on 7 September 2026; the first two returned zero studies, the third two studies unrelated to the substance. https://clinicaltrials.gov/
- Ma R, Lewis A (2020). Spadin selectively antagonizes arachidonic acid activation of TREK-1 channels. Frontiers in Pharmacology 11:434. PMID 32317978. DOI 10.3389/fphar.2020.00434
- Pietri M, Djillani A, Mazella J, Borsotto M, Heurteaux C (2019). First evidence of protective effects on stroke recovery and post-stroke depression induced by sortilin-derived peptides. Neuropharmacology 158:107715. PMID 31325429. DOI 10.1016/j.neuropharm.2019.107715. Abstract only; the full text is behind a publisher paywall.
- World Anti-Doping Agency. The 2026 Prohibited List; full text searched for "spadin", "PE 22", "TREK" and "potassium channel" with no match; class S0 wording quoted from the official text. Retrieved 7 September 2026.
- PubChem. Compound CID 165437303, "PE 22-28". Retrieved via the PUG-REST interface on 7 September 2026. The query only matches the spelling with a space, not with hyphens. https://pubchem.ncbi.nlm.nih.gov/compound/165437303
- UniProt Q99523, SORT1_HUMAN. Propeptide feature covering residues 34 to 77 of the precursor. Retrieved 7 September 2026; positions 12 to 28 and 22 to 28 recalculated from that sequence. https://rest.uniprot.org/uniprotkb/Q99523
- Mazella J, Pétrault O, Lucas G, et al. (2010). Spadin, a sortilin-derived peptide, targeting rodent TREK-1 channels: a new concept in the antidepressant drug design. PLoS Biology 8(4):e1000355. PMID 20405001. DOI 10.1371/journal.pbio.1000355
- Mazella J, Borsotto M, Heurteaux C (2018). The involvement of sortilin/NTSR3 in depression as the progenitor of spadin and its role in the membrane expression of TREK-1. Frontiers in Pharmacology 9:1541. PMID 30670975. DOI 10.3389/fphar.2018.01541. States that the sequence 22-28 is "called mini-spadin".
- European patent EP3526244B1, "Peptides derived from the propeptide NTSR3 and their use in the treatment of depression". Applicants CNRS and Université de Nice Sophia Antipolis; priority 11 October 2016, granted 6 September 2023, expected expiry 11 October 2037; GVSWGLR claimed as SEQ ID NO: 3. Retrieved 7 September 2026. https://patents.google.com/patent/EP3526244B1/en
- Devader C, Khayachi A, Veyssière J, et al. (2015). In vitro and in vivo regulation of synaptogenesis by the novel antidepressant spadin. British Journal of Pharmacology 172(10):2604-2617. PMID 25598009. DOI 10.1111/bph.13083
- Hivelin C, Béraud-Dufour S, Devader C, et al. (2016). Potentiation of calcium influx and insulin secretion in pancreatic beta cell by the specific TREK-1 blocker spadin. Journal of Diabetes Research 2016:3142175. PMID 28105440. DOI 10.1155/2016/3142175
- Kassan A, et al. (2021). Sortilin-derived peptides promote pancreatic beta-cell survival through CREB signaling pathway. Pharmacological Research 167:105539. PMID 33737242. DOI 10.1016/j.phrs.2021.105539
- Heurteaux C, Lucas G, Guy N, et al. (2006). Deletion of the background potassium channel TREK-1 results in a depression-resistant phenotype. Nature Neuroscience 9(9):1134-1141. PMID 16906152. DOI 10.1038/nn1749
- Devader C, Roulot M, Moréno S, et al. (2017). Serum sortilin-derived propeptides concentrations are decreased in major depressive disorder patients. Journal of Affective Disorders 208:443-449. PMID 27838145. DOI 10.1016/j.jad.2016.10.049
- Roulot M, Minelli A, Bortolomasi M, et al. (2018). Increased serum levels of sortilin-derived propeptide after electroconvulsive therapy in treatment-resistant depressed patients. Neuropsychiatric Disease and Treatment 14:2307-2312. PMID 30233189. DOI 10.2147/NDT.S170165
- Mazella J, et al. (2025). Serum sortilin-derived propeptide concentrations as markers of depression in chronic stroke. Journal of the Neurological Sciences 472:123459. PMID 40107034. DOI 10.1016/j.jns.2025.123459. STROKDEM cohort, registry entry NCT01330160.
- Qi X, Xu H, Wang L, Zhang Z (2018). Comparison of therapeutic effects of TREK1 blockers and fluoxetine on chronic unpredicted mild stress sensitive rats. ACS Chemical Neuroscience 9(11):2717-2724. PMID 29952548. DOI 10.1021/acschemneuro.8b00225
- Wu F, Sun H, Gong W, et al. (2021). Genetic and pharmacological inhibition of two-pore domain potassium channel TREK-1 alters depression-related behaviors and neuronal plasticity in the hippocampus in mice. CNS Neuroscience & Therapeutics 27(2):220-232. PMID 32864894. DOI 10.1111/cns.13450
- US Food and Drug Administration. Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks. Page current as of 22 April 2026; full text searched for "spadin" on 7 September 2026 with no match, while BPC-157, KPV and ipamorelin appear by name. https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks
- US Food and Drug Administration. Bulk Drug Substances Used in Compounding Under Section 503A of the FD&C Act. Page current as of 14 May 2026; full text searched for "spadin" on 7 September 2026 with no match. https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act
- García G, Martínez-Rojas VA, Murbartián J, et al. (2021). TREK-1 potassium channels participate in acute and long-lasting nociceptive hypersensitivity induced by formalin in rats. Behavioural Brain Research 409:113446. PMID 34224765. DOI 10.1016/j.bbr.2021.113446
- Moha Ou Maati H, Veyssiere J, Labbal F, et al. (2012). Spadin as a new antidepressant: absence of TREK-1-related side effects. Neuropharmacology 62(1):278-288. PMID 21807005. DOI 10.1016/j.neuropharm.2011.07.019
- Commercial product page for a PE-22-28 nasal spray, peptidedeck.com, read in full on 7 September 2026; further offerings recorded from search results only and not verified in full text. Cited as evidence that the product exists and how it is advertised, not as a technical source.
- US patent application US20240294603A1, "Systems and methods for delivery of spadin for treatment of depression or other indications". Applicant Transdermal Biotechnology, Inc.; published 5 September 2024, legal status abandoned. GVSWGLR appears as SEQ ID NO: 12; the claimed route is application to the skin. Retrieved 7 September 2026. https://patents.google.com/patent/US20240294603A1/en
- NCAA. Banned Substances; the list is stated to be neither complete nor exhaustive, and does not name the peptide. Retrieved 7 September 2026.
- Product information for Selank nasal drops, marketing authorisation holder AO INPZ Peptogen, Moscow, held in the Russian medicines database RLS, and the corresponding entry in the State Register of Medicines of the Russian Federation. Retrieved 6 September 2026. https://www.rlsnet.ru/drugs/selank-36612
- Vidal Russia, product information for Semax 0.1% nasal drops, registration ЛП-№(009449)-(РГ-RU) of 26 March 2025, marketing authorisation holder Peptogen, Moscow. Retrieved 6 September 2026. https://www.vidal.ru/drugs/semax__28676
- Djillani A, Pietri M, Mazella J, Heurteaux C, Borsotto M (2019). Fighting against depression with TREK-1 blockers: past and future. A focus on spadin. Pharmacology & Therapeutics 194:185-198. PMID 30291907. DOI 10.1016/j.pharmthera.2018.10.003
- Song Y, Song Y, Du W, et al. (2026). TREK-1 channel blockade mediates the antidepressant-like effects of hydroxynorketamine. Neuropharmacology 278:110751. PMID 41167417. DOI 10.1016/j.neuropharm.2025.110751
- PubChem. Compound CID 91826106, "Spadin". Formula C96H142N26O22, 2012.3 g/mol, corresponding to 18 residues including the tyrosine added for radioactive labelling. Retrieved 7 September 2026. https://pubchem.ncbi.nlm.nih.gov/compound/91826106
Cite this page
The facts on this page were checked on 7 September 2026, and every register and authority search behind the status table was run on that date. Because the entire evidence base rests on one research group and one main paper, a single new publication could change the picture substantially.
myPeptides Research & Editing. (2026). PE-22-28: what the studies show, status and safety. Version 1.0, 7 September 2026. myPeptides Peptide Register. Retrieved from https://mypep.app/peptides/pe-22-28
How pages in this register are compiled and graded is described under methodology; the full register is at peptides.
| Version | Date | Note |
|---|---|---|
| 1.0 | 7 September 2026 | Initial publication |