Informational only. Not medical advice.INFORMATIONAL PLATFORM ONLY — NOT MEDICAL ADVICE, DIAGNOSIS, OR TREATMENT
Informational only. Not medical advice.INFORMATIONAL PLATFORM ONLY — NOT MEDICAL ADVICE, DIAGNOSIS, OR TREATMENT
Head-to-head comparison of PE-22-28 and Semax — mechanism, dosing, side effects, legal status, and pricing.
PE-22-28 is a 7-amino-acid synthetic analog of spadin, a peptide fragment (residues 22-28) of the 44-aa propeptide (PE) released during post-translational maturation of sortilin (the neurotensin receptor-3). It is studied in preclinical models as a fast-acting antidepressant that works by selectively blocking the TREK-1 two-pore potassium channel. There is no established use for hair growth — that is a separate compound and the two should not be confused.
Semax is a synthetic heptapeptide (Met-Glu-His-Phe-Pro-Gly-Pro) derived from ACTH(4-10) with a Pro-Gly-Pro C-terminal extension for metabolic stability. It was developed at the Institute of Molecular Genetics (Russian Academy of Sciences) and registered as a drug in Russia in 1994. It is not FDA-approved.
PE-22-28
Semax
Category
Legal Status
Mechanism
Dose Range
Route
Frequency
COA-verified vendors · trust score ≥70 required · single-vial price — bulk/bundle deals may be lower
PE-22-28
Semax
COA corpus from Disclosed Labs — independently tested batches only.
PE-22-28
13
COAs
99.6%
Avg purity
7
Labs
Semax
82
COAs
99.5%
Avg purity
16
Labs
Mazella, Borsotto and colleagues at Nice, France identified spadin (Mazella et al., PLoS Biology 2010, PMID 20405001) and subsequently developed shortened PE 22-28 analogs with ~300× improved TREK-1 affinity and longer in vivo half-life (Djillani et al., Front Pharmacol 2017, PMID 28955242). In mouse antidepressant assays (forced swim, tail suspension, novelty-suppressed feeding), acute or 4-day IP dosing at ~3–4 μg/kg produced effects comparable to chronic SSRI treatment; oral gavage at 1 mg/kg was also active. The G/A-PE 22-28 modification extended duration of action to ~21–23 hours. Chronic dosing did not produce cardiac or seizure signals in rodents. No human clinical trials have been conducted. A detailed review of TREK-1 blockers for depression is available in Djillani et al., Pharmacol Ther 2019 (PMID 30291907).
Key references
Semax's evidence base is primarily Russian-language clinical literature. Gusev, Skvortsova and colleagues reported improved neurological recovery in acute hemispheric ischemic stroke when Semax was added to conventional therapy (Zh Nevrol Psikhiatr, 1997; PMID 11517472), and subsequent Russian studies extended use to cerebrovascular insufficiency (PMID 15792140). Preclinical work by Dolotov, Myasoedov and colleagues demonstrated that intranasal Semax rapidly elevates BDNF protein and TrkB activation in rat hippocampus and basal forebrain (Brain Res 2006, PMID 16996037; J Neurochem 2006, PMID 16635254). Genome-wide transcriptional analysis by Medvedeva et al. in rat focal ischemia showed Semax modulates a broad panel of immune-response and vascular-system genes (BMC Genomics 2014, PMID 24661604). Western evidence is limited; Semax has not been evaluated by the FDA and has no pivotal trials in the US or EU.
PE-22-28 and Semax are both in the Cognitive category and may have overlapping mechanisms. Researchers should review both profiles carefully, understand the mechanisms of action, and monitor the relevant biomarkers when combining compounds in the same class. As always, consult a licensed healthcare provider before making any decisions about combining research compounds.
This platform provides informational tools only, not medical advice. This comparison is for educational purposes only. Consult a licensed provider.
Dosing Notes
Half-life
Side Effects
Contraindications
Lab Testing
Key references
Disclosed Labs