PE-22-28 vs NA-Selank Amidate
Comprehensive side-by-side comparison of mechanisms, dosing, side effects, and research
Also: PE22-28, Spadin Analog
PE-22-28 is a seven-amino-acid peptide that blocks a potassium channel in the brain called TREK-1, the same target tied to depression. It is a shortened, more potent and more stable version of spadin, a natural fragment cut from the sortilin propeptide, and it was built to act like a fast antidepressant. All evidence is from rodents. There are no human clinical trials.
Also: N-Acetyl Selank Amidate, NA-Selank
NA-Selank Amidate is a chemically stabilized version of Selank, a Russian anxiolytic peptide derived from the immune fragment tuftsin. The acetyl group on one end and the amide on the other are there to slow enzymatic breakdown, which is a real and sensible modification. What has not been established is whether that translates into a meaningfully better result than plain Selank in humans.
Key Comparison Insights
- Both peptides belong to the Cognitive category, suggesting similar primary applications.
- NA-Selank Amidate has stronger research evidence (Human Trials) compared to PE-22-28 (Animal Studies).
Detailed Comparison
| Attribute | PE-22-28 | NA-Selank Amidate |
|---|---|---|
| Category | Cognitive | Cognitive |
| FDA Status | Not FDA Approved | Not FDA Approved |
| Clinical Status | Pre I II III IV FDA | Pre I II III IV FDA |
| Mechanism of Action | PE-22-28 inhibits TREK-1, a two-pore-domain potassium channel that normally lets potassium leak out of neurons and quiets them down. Block that leak and serotonin-producing neurons in mood-related regions become easier to fire, which is the proposed antidepressant mechanism. This is the same pathway implicated in why TREK-1 knockout mice show a depression-resistant phenotype. Compared to the parent peptide spadin, PE-22-28 binds TREK-1 far more tightly and survives much longer in the body, which is why it was developed. Whether TREK-1 blockade translates into a real antidepressant effect in people remains unproven. | Selank is a synthetic analog of tuftsin, a naturally occurring immunomodulatory peptide fragment. Its reported mechanism has two strands. The first is modulation of GABAergic signalling, which is the basis of its anxiolytic reputation, achieved without the sedation, tolerance or dependence associated with benzodiazepines. The second is an effect on the balance of monoamines and on BDNF expression, which is where the cognitive and mood claims come from. It also retains some of tuftsin's immunomodulatory activity, including effects on interleukin expression. The N-acetylation and C-terminal amidation in this version block the exopeptidases that would otherwise clip the peptide quickly, extending how long it survives after administration. That is a pharmacokinetic change, not a new mechanism. |
| Common Dosing | 100-300 mcg intranasal or subcutaneous Once daily | 250-500 mcg daily (intranasal) Once or twice daily |
| Administration | Intranasal or subcutaneous injection | Intranasal is the standard route. Subcutaneous is reported but less common. |
| Typical Duration | Research protocols vary, often 2-4 weeks | Community protocols commonly report 2-4 weeks, though Selank's clinical use does not indicate a dependence risk requiring cycling |
| Best Time to Take | Morning | Morning or split across the day |
Possible Side Effects May vary by individual |
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| Research Summary | The core data come from a single 2017 paper by Djillani and colleagues in Frontiers in Pharmacology, which screened shortened spadin analogs and found PE-22-28 to be the standout: dramatically stronger TREK-1 inhibition, longer in vivo stability, and antidepressant-like behavior in mice using standard tests like the forced swim and novelty-suppressed feeding paradigms. The same line of work reported that short treatment courses increased hippocampal neurogenesis in rodents, which the authors framed as a possible mechanism for faster mood effects than conventional SSRIs. The broader TREK-1 and spadin story traces back to Mazella et al. in 2010, who first described spadin as a natural antidepressant-type TREK-1 blocker. Importantly, every result is preclinical and in animals. There are no completed or published human efficacy or safety trials of PE-22-28, and it is not an approved drug anywhere. Claims that it treats depression, anxiety, or cognitive decline in people go well beyond what the evidence supports. | Selank itself has a real research base, almost all of it Russian, including clinical work in generalised anxiety disorder where it performed comparably to benzodiazepines without the sedation and withdrawal profile, plus animal work supporting the BDNF and monoamine effects. That literature is genuine but it is largely published in Russian journals, has not been replicated in large Western trials, and has not been through FDA or EMA assessment. The amidate variant specifically has essentially no independent published pharmacology. The stability argument is chemically sound and is the same modification used across many research peptides, but nobody has published a human comparison showing it outperforms standard Selank at equivalent doses. Treat the parent compound's evidence as real but geographically narrow, and the variant's advantage as plausible rather than demonstrated. |
Frequently Asked Questions: PE-22-28 vs NA-Selank Amidate
What is the difference between PE-22-28 and NA-Selank Amidate?
PE-22-28 is a cognitive peptide that pe-22-28 is a seven-amino-acid peptide that blocks a potassium channel in the brain called trek-1, the same target tied to depression. it is a shortened, more potent and more stable version of spadin, a natural fragment cut from the sortilin propeptide, and it was built to act like a fast antidepressant. all evidence is from rodents. there are no human clinical trials. NA-Selank Amidate is a cognitive peptide that na-selank amidate is a chemically stabilized version of selank, a russian anxiolytic peptide derived from the immune fragment tuftsin. the acetyl group on one end and the amide on the other are there to slow enzymatic breakdown, which is a real and sensible modification. what has not been established is whether that translates into a meaningfully better result than plain selank in humans. The main differences lie in their mechanisms of action and clinical applications.
Which is better, PE-22-28 or NA-Selank Amidate?
Neither is universally "better" - the choice depends on your specific goals. PE-22-28 is typically used for cognitive purposes, while NA-Selank Amidate is used for cognitive. Always consult with a healthcare provider to determine which may be appropriate for your situation.
Can PE-22-28 and NA-Selank Amidate be used together?
Some peptide protocols combine multiple compounds for synergistic effects. However, using PE-22-28 and NA-Selank Amidate together should only be considered under medical supervision, as both compounds have their own side effect profiles and potential interactions. Research on their combined use may be limited.