Semax

Semax is a synthetic heptapeptide (Met-Glu-His-Phe-Pro-Gly-Pro) built from the 4-10 fragment of adrenocorticotropic hormone (ACTH), engineered by Russian researchers at the Institute of Molecular Genetics to retain the neuroactive character of the parent ACTH fragment while eliminating its hormonal, steroidogenic activity. Rather than acting through classical corticotropin receptors, Semax is studied for its capacity to upregulate brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) expression in the hippocampus and frontal cortex, making it a research subject in neurotrophin signaling, synaptic plasticity, and neuroprotection models. Its distinctive research profile stems from a short plasma half-life paired with disproportionately long-lasting central effects, and from its frequent administration via intranasal routes in animal studies, a route that bypasses first-pass metabolism and allows direct assessment of nose-to-brain peptide delivery and regional neurotrophin dynamics across brain structures. Peptides.SO currently aggregates 151 supplier listings for Semax from 95 distinct vendors, 151 of them in stock as of September 2026; across the 49 listings whose quantities normalize to a per-milligram basis the median price is $4.50/mg, with the middle half of the market between $2.80 and $6.40/mg.

Mechanism of Action:

Semax's primary research interest centers on its neurotrophin-upregulating activity. Studies in rodents have shown that Semax administration increases mRNA and protein levels of BDNF and NGF in the hippocampus, frontal cortex, and retinal ganglion cells — neurotrophins critical to synaptic plasticity, long-term potentiation, and neuronal survival. The mechanism by which a short heptapeptide drives these changes is not fully characterized, but proposals include indirect modulation of serotonergic and dopaminergic tone (which are known transcriptional regulators of BDNF expression), effects on monoamine oxidase activity, and possible interaction with melanocortin receptor subtypes that do not drive the classical steroidogenic cascade. The Pro-Gly-Pro C-terminal extension appended to the ACTH(4-7) core sequence is critical for metabolic stability: it blocks exopeptidase degradation that would otherwise reduce the native ACTH(4-10) fragment to an inactive remnant within minutes. The intranasal route explored in many Semax studies takes advantage of olfactory receptor neuron uptake and axonal transport to achieve direct CNS exposure, circumventing the blood-brain barrier limitation that constrains many larger peptides.

Key Research Studies:

Shadrina MI et al. compared temporal dynamics of NGF and BDNF gene expression in rat hippocampus, frontal cortex, and retina following Semax administration, documenting significant upregulation in all three tissues over a 24-hour post-injection window — a time course that far exceeds the measurable plasma half-life of the peptide, supporting a transcriptional rather than receptor-occupancy mechanism for its lasting effects. PubMed PMID: 19662538.

Lebedeva IS et al. used fMRI to examine regional brain activity differences in healthy volunteers following Semax nasal drops versus placebo, observing changes in prefrontal and temporal cortex activation patterns during cognitive tasks, providing early translational data on Semax's central pharmacological activity in humans. PubMed PMID: 18414765.

Inozemtseva LS et al. reported antidepressant-like and antistress effects of Semax (alongside Melanotan II) in male rats exposed to chronic unpredictable stress, with significant attenuation of immobility in forced swim test and sucrose preference measures, adding behavioral pharmacology data relevant to mood-related neurotrophin research. PubMed PMID: 39442746.

Dolotov OV et al. demonstrated neuroprotective effects of Semax in rat and gerbil models of cerebral ischemia-reperfusion injury, with reductions in infarct volume and behavioral deficit measures associated with preservation of BDNF expression in ischemic penumbra tissue. PubMed PMID: 16819520.

Research Concentrations Used in Studies:

Animal studies typically employ intranasal doses of 25–50 mcg/kg body weight per administration, dissolved in normal saline at concentrations of 0.1–1.0% (1–10 mg/mL). Systemic injection protocols in rodents have used doses of 0.05–0.5 mg/kg. Reconstituted solutions at 1 mg/mL in sterile saline or bacteriostatic water are stable for 7–14 days at 4°C. The peptide is soluble in aqueous solution at physiological pH with minimal precipitation concerns. For intranasal delivery studies, pH adjustment to 5.5–7.0 is maintained to match the nasal mucosal environment.

Potential Research Applications:

Cognitive performance and learning-memory models using Morris water maze and novel object recognition assays BDNF and NGF gene expression regulation in hippocampus and prefrontal cortex Neuroprotection in cerebral ischemia, stroke, and excitotoxicity models Intranasal peptide delivery and nose-to-brain transport research and bioavailability studies Stress-response and antidepressant-like behavior assays (forced swim, sucrose preference, open field) Retinal and optic nerve neurotrophin dynamics in models of retinal degeneration Monoamine neurotransmitter system modulation studies Synaptic plasticity and long-term potentiation research in hippocampal slice preparations

Safety Profile from Published Research:

Semax has an extended safety record from Russian clinical use, where it has been evaluated in human subjects for stroke rehabilitation and cognitive applications under regulatory frameworks differing from FDA/EMA standards. Preclinical rodent studies report no overt toxicity at standard research doses; the peptide does not bind classical corticotropin receptors and therefore does not drive ACTH-related adrenal effects or hypothalamic-pituitary-adrenal axis suppression. The most commonly noted adverse signal in rodent studies is transient behavioral activation (hyperlocomotion) at higher doses, consistent with monoaminergic stimulation. No carcinogenicity or reproductive toxicity data meeting modern regulatory standards exists in the peer-reviewed literature for Semax. For research use only; not for human or veterinary administration.

Marketplace Snapshot (September 2026, Peptides.SO listings data): Tracked listings: 151 from 95 distinct suppliers (151 in stock) Listings with a verifiable per-mg price: 49 Median price per mg: $4.50 (interquartile range $2.80 to $6.40) Lowest verified per-mg price: $1.33/mg (Top Peptides: $34.99 for 26.3 mg) Top Peptides: $34.99 for 26.3 mg ($1.33/mg) Buy Peptides USA: $42.99 for 30.1 mg ($1.43/mg) Liberty Peptides: $56.00 for 29.9 mg ($1.87/mg) Listings that price by kit, bundle, or unit rather than by weight cannot be normalized to a per-mg basis and are excluded from the figures above. Prices change frequently; the live comparison table on this page reflects the most recent crawl.

Frequently Asked Questions:

Q: How many suppliers list Semax on Peptides.SO, and what does it typically cost? A: Peptides.SO tracks 151 Semax listings from 95 distinct suppliers, all currently marked in stock. Across the 49 listings that publish a quantity we can normalize to a per-milligram basis, the median works out to $4.50/mg, with the middle half of the market falling between $2.80 and $6.40/mg.

Q: Why do per-milligram prices for Semax vary by more than a factor of four? A: Three factors account for most of the spread: vial size (larger multi-vial packs almost always lower the per-mg figure), whether the supplier publishes batch-specific third-party analysis, and whether the listed price is a standing price or a promotional one. Listings that bundle several vials or advertise per-kit rather than per-mg pricing cannot be normalized reliably and are excluded from the statistics above.

Q: What distinguishes Semax from the unmodified ACTH(4-10) fragment? A: Semax appends a Pro-Gly-Pro tail to the ACTH(4-10) sequence. That C-terminal extension markedly slows enzymatic degradation relative to the bare fragment while leaving the neuroactive character intact, which is why research models report central effects that outlast the peptide's short measured plasma half-life.

Q: What documentation should a research buyer request before purchasing? A: A batch-specific certificate of analysis with both HPLC purity and mass-spectrometry identity confirmation, dated and traceable to the lot being shipped. Generic or undated COAs, and COAs that report purity without confirming molecular weight, provide substantially weaker assurance.

Q: How does Semax compare with Selank as a research subject? A: Both are Russian-developed short peptides studied in rodent behavioral models, but they derive from different parent molecules and are investigated for different endpoints: Semax from ACTH(4-10) with a neurotrophin (BDNF/NGF) emphasis, Selank from tuftsin with an anxiolytic-like and immunomodulatory emphasis.

Q: Why are Semax's central effects longer-lasting than its plasma half-life would predict? A: The prevailing explanation is a transcriptional mechanism: Semax triggers sustained BDNF/NGF gene upregulation that persists well after the peptide itself has cleared. Additionally, the intranasal route may enable local axonal uptake in olfactory neurons that creates a depot effect in the CNS, sustaining receptor interactions beyond what systemic pharmacokinetics would indicate.

Q: Is Semax approved for human use? A: No. Material listed on this platform is unapproved research chemical supply sold strictly for in-vitro and preclinical laboratory investigation. It is not a drug, is not approved by the FDA for any indication, and is not for human or veterinary consumption.

Related Research on Peptides.SO: peptides.so/learn/neuroprotective-peptides-compared-semax-selank-dihexa-p21 peptides.so/peptide/selank peptides.so/learn/peptide-purity-testing-hplc-mass-spec peptides.so/tools/calculator peptides.so/learn/peptide-storage-best-practices

Cited Research: Shadrina M, Kolomin T, Agapova T, et al. Comparison of the temporary dynamics of NGF and BDNF gene expression in rat hippocampus, frontal cortex, and retina under Semax action. Journal of Molecular Neuroscience. 2010. PubMed PMID: 19662538. Inozemtseva LS, Yatsenko KA, Glazova NY, et al. Antidepressant-like and antistress effects of the ACTH(4-10) synthetic analogs Semax and Melanotan II on male rats in a model of chronic unpredictable stress. European Journal of Pharmacology. 2024. PubMed PMID: 39442746. Lebedeva IS, Panikratova YR, Sokolov OY, et al. Effects of Semax on the Default Mode Network of the Brain. Bulletin of Experimental Biology and Medicine. 2018. PubMed PMID: 18414765. Dolotov OV, Karpenko EA, Inozemtseva LS, et al. Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. Brain Research. 2006. PubMed PMID: 16819520.

For laboratory research only. Not for human or veterinary use, diagnosis, treatment, cure, or prevention of any disease. THIS PRODUCT IS NOT FOR HUMAN CONSUMPTION.