Compounds / PE-22-28
PE-22-28
Also known as: PE 22-28; mini-spadin; shortened spadin analog; spadin-derived TREK-1 blocker
Primary research focus: Antidepressant and neurogenesis research (TREK-1 potassium channel blocker)
Last updated July 2026 · Reviewed against FDA labeling and published research.
What is PE-22-28?
PE-22-28 is a synthetic seven-amino-acid peptide engineered as a shortened, more potent analog of spadin, a naturally occurring peptide cleaved from the sortilin propeptide. It blocks the TREK-1 potassium channel, a mechanism linked to rapid antidepressant-like effects in rodent models. It was designed by studying spadin's blood degradation products to identify the minimal active fragment. All evidence is preclinical: there are no human clinical trials, and it is not FDA-approved.
TREK-1 (TWIK-related potassium channel 1) is a two-pore-domain potassium channel abundant in the hippocampus and cortex that contributes background potassium currents shaping neuronal resting potential and excitability. Mice lacking TREK-1 are resistant to depressive-like states, which made channel blockade an antidepressant target. Spadin was identified as an endogenous TREK-1 blocker with antidepressant-like activity; PE-22-28 spans residues 22 to 28 of spadin and blocks TREK-1 with substantially greater potency (reported IC50 of approximately 0.12 nM versus roughly 40 to 60 nM for spadin, an order-of-magnitude improvement) and better in vivo stability. Preclinically it also stimulates adult hippocampal neurogenesis and synaptogenesis within a few days, faster than the weeks required by conventional antidepressants. This mechanism is established in rodent and cell systems only; it is not confirmed in humans.
How it’s supplied
Not an FDA-approved or commercially manufactured medicine. It is sold as a research-grade lyophilized peptide for reconstitution, often marketed for intranasal or subcutaneous research use. Research-grade products are not FDA-reviewed for identity, potency, or sterility, and there is no legal commercial or clinical pathway.
Dosage Chart
Units shown are for a U-100 insulin syringe (100 units = 1 mL), calculated from the vial size and BAC water you select. Always confirm against your prescription and your syringe markings.
| Phase | Dose | Frequency | Notes |
|---|---|---|---|
| Weeks 1-4 | 50mcg | 1x Daily | — |
| Weeks 5-8 | 100mcg | 1x Daily | — |
| Weeks 9-12 | 150mcg | 1x Daily | — |
| Weeks 13-16 | 200mcg | 1x Daily | — |
- Rotate injection sites to reduce irritation and lipohypertrophy
- Not for use during pregnancy or breastfeeding
- Do not exceed the recommended dose to try to speed results
Potential Benefits and Side Effects
Effects reported in published research. Not a promise of results, and not medical advice.
- Reported in preclinical (rodent and cell) research only; human efficacy is not established.
- Potent and selective TREK-1 channel blockade (reported IC50 approximately 0.12 nM, roughly 300-fold more potent than spadin).
- Antidepressant-like activity in rodent models (reduced immobility in forced swim and tail suspension tests).
- Stimulation of adult hippocampal neurogenesis and synaptogenesis within days in animal models.
- Improved in vivo stability and duration compared with the parent peptide spadin.
- No human adverse-effect data are available.
- Rodent studies have not reported the sexual dysfunction, weight gain, or sedation associated with conventional antidepressants, but this is an animal observation, not a human finding.
- Human tolerability and long-term safety are entirely uncharacterized.
Warnings and contraindications
Important safety information. This is not exhaustive — read the full prescribing information and consult your prescriber or pharmacist.
- No FDA-approved labeling exists; the following reflect the compound's status and the limits of its evidence, not established label warnings.
- There are no human clinical trials of PE-22-28; no human safety, efficacy, dosing, or bioavailability data exist.
- Rodent behavioral models (such as the forced swim test) screen for antidepressant-like activity but do not establish treatment of depression in people.
- It should not be described or used as a treatment for depression, anxiety, stroke, or cognitive impairment; no regulator-approved labeling or human evidence supports that.
- Depression is a serious condition with effective evidence-based treatments; substituting an unstudied research peptide carries real risk.
- Research-grade material varies in identity and purity; safety in pregnancy and breastfeeding has not been studied.
- Not established; no FDA-approved labeling. Precautionary considerations include known hypersensitivity and any condition where altering neuronal excitability could be harmful (for example, seizure disorders), on theoretical grounds.
Reconstitution Steps
How to prepare the lyophilized vial. Confirm specifics with your pharmacist or prescriber.
- Confirm the amount of peptide in the vial and the volume of diluent you intend to use before starting.
- Wash your hands and gather supplies: the lyophilized vial, the diluent (typically bacteriostatic water), an alcohol swab, and a sterile syringe.
- Let the vial and diluent reach room temperature if they were refrigerated or frozen.
- Wipe the rubber stopper of both the peptide vial and the diluent vial with a fresh alcohol swab and let them air dry.
- Draw the intended diluent volume into the syringe.
- Insert the needle into the vial and slowly release the diluent down the inside wall rather than directly onto the powder, to avoid foaming.
- Do not shake. Gently swirl or roll the vial until fully dissolved.
- Inspect the solution: it should be clear and colorless with no visible particles. Do not use if cloudy or containing particles.
- Note the resulting concentration (amount divided by diluent volume) so it matches the reconstitution calculator on this page.
- Label the vial with the reconstitution date and store as directed under reconstituted storage.
US regulatory status
Classifications are public record but can change. For reference only, not legal advice.
Development: The TREK-1 antidepressant hypothesis originates with Mazella and colleagues, who described spadin (PE 12-28) around 2010 as an endogenous peptide cleaved from the sortilin propeptide that selectively blocks TREK-1 and produces antidepressant-like effects in mice. Spadin's short duration of action (activity gone beyond about 7 hours) and modest affinity limited it. Djillani and colleagues (Frontiers in Pharmacology, 2017) analyzed spadin's blood degradation products by HPLC and used that to design shortened analogs, identifying PE-22-28 as the shortest, most efficient sequence blocking TREK-1, with roughly 300-fold greater potency and improved stability, while retaining antidepressant activity in acute and sub-chronic rodent dosing. PE-22-28 was then used as a core scaffold for further analogs with modified termini. Despite an attractive mechanism, no sponsor has advanced PE-22-28 into human trials; no clinical trial has been completed or registered as of 2026, and there is no FDA approval or IND.
Notes: PE-22-28 is not FDA-approved and has no recognized clinical use. It has no IND and no completed or registered human clinical trial, and is sold only as a research chemical through gray-market vendors, outside FDA quality oversight. It is not on the FDA 503A bulk drug substances list and is not eligible for 503A or 503B compounding. It is not a controlled substance.
International status
Pharmacokinetics
Storage and handling
Important Notes
Practical considerations for consistency and safety.
- All PE-22-28 evidence is preclinical; there are no human trials, no human safety data, and no established dose.
- It is a shortened analog of spadin (PE 12-28), which derives from the sortilin propeptide; some vendor descriptions incorrectly trace it to PACAP or claim additional receptor activity not supported by the primary literature.
- Sources disagree on its exact length and sequence; verify against the certificate of analysis.
- Rodent forced-swim-test activity is a screening signal, not evidence of treating depression in people.
- Anyone experiencing depression should seek evidence-based care rather than an unstudied research peptide.
Lifestyle Factors
- Studied only in laboratory settings.
- Human lifestyle interactions are unstudied.
References
Related compounds
Important disclaimer
This page is an educational reference, not medical advice, a diagnosis, or a treatment recommendation, and not a substitute for your prescriber or pharmacist. Approval and regulatory status varies by compound and can change. Always confirm against current prescribing information and consult a qualified healthcare professional before making any decision about a medication.