Educational reference, not medical advice. This page summarizes information from published research and regulatory filings for educational purposes. It is not a recommendation to use any compound and should not replace guidance from a licensed healthcare provider. Most peptides discussed here are not approved for the uses described.
What it is
Semax is a synthetic heptapeptide with the sequence Met-Glu-His-Phe-Pro-Gly-Pro (MEHFPGP). The first four residues correspond to amino acids 4 through 7 of adrenocorticotropic hormone (ACTH), and the C-terminal Pro-Gly-Pro extension was added by the Russian developers to confer enzymatic stability without restoring hormonal (corticosteroid-releasing) activity. The result is a peptide that retains the neurotrophic and behavioral effects associated with ACTH(4-10) but lacks the systemic endocrine effects of native ACTH.
Semax is administered as an intranasal solution. The standard formulations approved in Russia are 0.1% and 1% nasal drops marketed under the trade name Semax (and Semax 1% under the brand Semax Pro). The peptide is taken up through the nasal mucosa, in part by direct nose-to-brain transport along the olfactory and trigeminal pathways.
History
The peptide was designed in the early 1980s at the Institute of Molecular Genetics of the Russian Academy of Sciences. The clinical development was carried out in collaboration with the Russian Ministry of Health and culminated in approval by the Russian regulator in the 1990s. Approvals followed in Ukraine and several other former-Soviet jurisdictions.
The bulk of the published mechanism literature was generated by Dolotov, Myasoedov, Grivennikov, and colleagues, with key papers in the mid-2000s demonstrating that intranasal Semax increases BDNF protein in rat basal forebrain and hippocampus and modulates TrkB receptor expression. Behavioral studies in rodent models have examined effects on learning, attention, and stress-induced behavioral changes.
Regulatory status
Semax is approved in Russia, Ukraine, Belarus, and Georgia for a set of cerebrovascular and cognitive indications, including ischemic stroke (Semax 1%), transient ischemic attack, and disorders of attention and memory in adults (Semax 0.1%). It is dispensed by prescription in those jurisdictions.
Semax has not been approved by the FDA, EMA, MHRA, Health Canada, or the Therapeutic Goods Administration. It is sold internationally through research-chemical suppliers under not-for-human-use labeling and is not regulated as a pharmaceutical outside its approved markets.
Mechanism
The published mechanism papers describe Semax as a neurotrophic-pathway modulator rather than an agonist of any single classical receptor. The dominant findings:
- BDNF and TrkB upregulation. Multiple rodent studies report that intranasal Semax increases BDNF protein in the hippocampus and basal forebrain and modulates expression of its receptor TrkB.
- Modulation of monoamine systems. Semax has been reported to influence dopamine and serotonin turnover in striatum and cortex in rodents.
- Neuroprotection in ischemia models. In rodent middle cerebral artery occlusion models, Semax reduces infarct volume — the preclinical basis for the stroke indication.
These effects have been described primarily in rodents. Mechanistic data in human tissue is limited.
Half-life and dosing intervals
Semax in plasma has a very short half-life — published estimates put it in the range of 2 to 5 minutes after intranasal administration, with the heptapeptide rapidly hydrolyzed by serum aminopeptidases. The downstream BDNF and behavioral effects nonetheless persist for hours to days, which the authors attribute to triggering of downstream signaling rather than sustained peptide presence.
Russian dosing labels specify intranasal use. For Semax 0.1%, the labeled dose range studied is 200 to 2,000 micrograms per day divided across multiple intranasal administrations, with typical regimens delivering one to three drops per nostril two to three times daily. For Semax 1% (the higher-strength stroke formulation), the labeled range goes substantially higher and is reserved for acute hospital use.
Reconstitution example
Branded Semax is supplied as a ready-to-use intranasal solution and does not require reconstitution. Research-grade Semax is sold as a lyophilized powder, typically in 5 mg, 10 mg, or 30 mg vials. To produce an intranasal solution comparable to the 0.1% (1 mg/mL) commercial formulation, a 10 mg vial is reconstituted with 10 mL of bacteriostatic water or saline. One drop from a typical dropper (approximately 0.05 mL) then contains about 50 mcg.
What to know
- Limited Western data. Almost all published efficacy evidence comes from Russian-language journals and from rodent studies. There has been no Phase III trial registered with U.S. or EU regulators.
- Intranasal only. Semax was designed for intranasal use; subcutaneous and oral routes have been explored in research but are not part of the approved formulations.
- Reported adverse effects in the Russian labeling include local nasal irritation; systemic adverse effects are rare in the published data, but long-term safety has not been characterized in non-Russian populations.
- Storage. The intranasal solution is refrigerated. Lyophilized Semax should be refrigerated or frozen and protected from light; once reconstituted into solution, refrigerate and use within the stability window quoted by the supplier.
- No hormonal activity. Despite being derived from ACTH, Semax does not raise cortisol at standard doses — the design specifically removed the corticotropic portion of the parent molecule.
Sources
- 1.Dolotov OV, Karpenko EA, Inozemtseva LS, Seredenina TS, Levitskaya NG, Rozyczka J, Dolotov AV, Grivennikov IA, Andreeva LA, Myasoedov NF, Engele J (2006). Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of brain-derived neurotrophic factor protein in rat basal forebrain. Journal of Neurochemistry.
- 2.Dolotov OV, Karpenko EA, Seredenina TS, Inozemtseva LS, Levitskaya NG, Zolotarev YA, Kamensky AA, Grivennikov IA, Engele J, Myasoedov NF (2006). Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. Brain Research.
- 3.Dolotov OV, Seredenina TS, Levitskaya NG, et al. (2003). The heptapeptide SEMAX stimulates BDNF expression in different areas of the rat brain in vivo. Doklady Biological Sciences.
- 4.Yatsenko KA, Glazova NY, Inozemtseva LS, Andreeva LA, Kamensky AA, Grivennikov IA, Myasoedov NF, Dolotov OV (2013). Heptapeptide semax attenuates the effects of chronic unpredictable stress in rats. Doklady Biological Sciences.