Semax: Safety Profile & Research Summary
23 PubMed CitationsExpert ReviewedGMP CertifiedLast Reviewed: February 2026
Preclinical Research Summary
Animal Studies
| Model | Species | Key Findings | Ref |
|---|---|---|---|
| Alzheimer's (APP/PS1) | Transgenic mice | Plaque reduction 2.8× cortex, 2.6× hippocampus; cognitive restoration (p<0.0001) | [21] |
| Ischemic Stroke (tMCAO) | Wistar rats | 394 DEGs modulated; vascularization ↑1.25×, neuroglial proliferation ↑1.4× | [15] |
| Chronic Stress | Wistar rats | Corticosterone ↓28–34%; anxiety reduced at 50–150 μg/kg | [20] |
| Spinal Cord Injury | C57BL/6 mice | Improved Basso scores; μ-opioid / USP18 / FTO pathway | [22] |
| Cognitive Enhancement | Wistar rats | 1.4× hippocampal BDNF protein; 3× exon III BDNF mRNA; accelerated learning | [14] |
| Dopaminergic System | C57BL/6 mice | +25% striatal 5-HIAA; potentiated amphetamine-induced DA release | [1] |
| Ophthalmic | Wistar rats | Retinal microcirculation ↑ to 671.7 PU; improved ERG parameters | [24] |
| Maternal Deprivation | White rats | Normalized anxiety from early-life stress; compensated body weight loss | [25] |
Clinical Studies / Human Data
| Study | Design | n= | Key Outcome | Ref |
|---|---|---|---|---|
| Kaplan 1996 | Volunteers | — | Improved memory and attention lasting 20–24 hours | [18] |
| Russian Patent 1995 | Multi-condition | 303 | Enhanced selective attention, motivation, adaptive capability | [4] |
| Gusev 2005 | Clinical | 187 | Reduced stroke/TIA risk; stabilized disease progression | [5] |
| Gusev 1997/2018 | Clinical | — | Accelerated functional recovery, decreased inflammation (IL-10, CRP) | [7] |
| Polunin 2000 | Comparative | — | Improved visual acuity, expanded visual field | [19] |
| Kurysheva 2001 | Comparative | — | Superior to traditional neuroprotective protocols for glaucomatous neuropathy | [19] |
| Ivanikov 2002 | Comparative | — | 89.5% healing (Semax) vs 30.8% (control) at day 14 | [23] |
| Serdiuk 2007 | Clinical | 27 | Improved quality of life, mood, and cognition | [5] |
Pharmacokinetic Parameters
| Parameter | Value | Ref |
|---|---|---|
| Intranasal Bioavailability | 60–70% | [17] |
| Plasma Half-life | ~1–2 hours | [17] |
| Duration of Experimental Effects | 20–24 hours | [5] |
| BBB Penetration | Rapid CNS distribution | [17] |
| Receptor Binding (Kd) | 2.4 ± 1.0 nM (basal forebrain) | [9] |
| MC4/MC5 Activity | Competitive antagonist (α-MSH) | [11] |
| Enkephalinase Inhibition | IC₅₀ = 10 μM | [12] |
Comparison with Related Compounds
| Feature | Semax | Selank |
|---|---|---|
| Parent Molecule | ACTH(4-7) | Tuftsin |
| Sequence | MEHFPGP (7 aa) | TKPRPGP (7 aa) |
| Primary Focus | Nootropic / neuroprotection | Anxiolytic / immunomodulation |
| BDNF Induction | Strong (8× mRNA) | Moderate |
| Hormonal Activity | None | None |
| PGP Stabilizer | Yes | Yes |
| Russian Registration | Yes — stroke, cognition, optic nerve | Yes — anxiety disorders |
The products offered on this website are furnished for in-vitro studies only. In-vitro studies (Latin: in glass) are performed outside of the body. These products are not medicines or drugs and have not been approved by the FDA to prevent, treat or cure any medical condition, ailment or disease. Bodily introduction of any kind into humans or animals is strictly forbidden by law.
For Laboratory Research Only. Not for human use, medical use, diagnostic use, or veterinary use.
ALL ARTICLES AND PRODUCT INFORMATION PROVIDED ON THIS WEBSITE ARE FOR INFORMATIONAL AND EDUCATIONAL PURPOSES ONLY.
References
- Eremin KO, Kudrin VS, Saransaari P, Oja SS, Grivennikov IA, Myasoedov NF, Rayevsky KS. Semax, an ACTH(4-10) Analogue with Nootropic Properties, Activates Dopaminergic and Serotoninergic Brain Systems in Rodents. Neurochemical Research. 2005;30(12):1493–1500.
- Potaman VN, Alfeeva LY, Kamensky AA, Levitzkaya NG, Nezavibatko VN. N-terminal degradation of ACTH(4-10) and its synthetic analog semax by the rat blood enzymes. Biochem Biophys Res Commun. 1991;176(2):741–746.
- Ashmarin IP, Nezavibatko VN, Levitskaya NG, Koshelev VB, Kamensky AA. Design and investigation of an ACTH(4-10) analogue lacking D-amino acids and hydrophobic radicals. Neuroscience Research Communications. 1995;16(2):105–112.
- Ashmarin IP, Nezavibatko VN, Myasoedov NF, et al. A nootropic adrenocorticotropin analog 4-10-semax (15 years experience in its design and study). Zhurnal Vysshei Nervnoi Deiatelnosti. 1997;47(2):420–430.
- Gusev EI, Skvortsova VI, Chukanova EI. Semax in prevention of disease progress and development of exacerbations in patients with cerebrovascular insufficiency. Zhurnal Nevrologii i Psikhiatrii. 2005;105(2):35–40.
- U.S. Food and Drug Administration. Bulk Drug Substances Used in Compounding Under Section 503B. FDA Compounding Database. 2023.
- Gusev EI, Skvortsova VI, Myasoedov NF, et al. Effectiveness of Semax in acute period of hemispheric ischemic stroke. Zhurnal Nevrologii i Psikhiatrii. 1997;97(6):26–34.
- Kolomin TA, Shadrina M, Slominsky P, Limborska SA, Myasoedov NF. A New Generation of Drugs: Synthetic Peptides Based on Natural Regulatory Peptides. Neuroscience and Medicine. 2013;4(4):223–252.
- Dolotov OV, Karpenko EA, Seredenina TS, et al. Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of BDNF protein in rat basal forebrain. J Neurochem. 2006;97(Suppl 1):82–86.
- 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;1117(1):54–60.
- Levitskaya NG, Glazova NY, Sebentsova EA, et al. Investigation of the Spectrum of Physiological Activities of the Heptapeptide Semax. Neurochemical Journal. 2008;2(1–2):95–101.
- Shadrina MI, Dolotov OV, Grivennikov IA, et al. Rapid induction of neurotrophin mRNAs in rat glial cell cultures by Semax. Neuroscience Letters. 2001;308(2):115–118.
- Filippenkov IB, Stavchansky VV, Denisova AE, et al. Novel Insights into the Protective Properties of ACTH(4-7)PGP (Semax) Following Cerebral Ischaemia–Reperfusion in Rats. Genes. 2020;11(6):681.
- Medvedeva EV, Dmitrieva VG, Povarova OV, et al. The peptide semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia: genome-wide transcriptional analysis. BMC Genomics. 2014;15:228.
- Stavchansky VV, Yuzhakov VV, Botsina AY, et al. The Effect of Semax and Its C-End Peptide PGP on the Morphology and Proliferative Activity of Rat Brain Cells During Experimental Ischemia. J Mol Neurosci. 2011;45(2):177–185.
- Kaplan AY, Kochetova AG, Nezavibatko VN, Ryasina TV, Ashmarin IP. Synthetic ACTH analogue Semax displays nootropic-like activity in humans. Neuroscience Research Communications. 1996;19(2):115–123.
- Polunin GS, Nurieva SM, Bayandin DL, Sheremet NL. Evaluation of therapeutic effect of new Russian peptide drug Semax in optic nerve disease. Vestnik Oftalmologii. 2000;116(1):15–18.
- Vorvul AO, Bobyntsev II, Medvedeva OA, et al. Effects of Semax in conditions of acute and chronic social stress. Zhurnal Vysshei Nervnoi Deiatelnosti. 2021;71(4):560–570.
- Radchenko AI, Kuzubova EV, Apostol AA, et al. The Potential of the Peptide Drug Semax and Its Derivative for Correcting Pathological Impairments in the Animal Model of Alzheimer's Disease. Acta Naturae. 2025;17(4):110–120.
- Liu Y, et al. Semax improves spinal cord injury via μ-opioid receptor targeting USP18-mediated FTO deubiquitination. Front Cell Neurosci. 2025.
- Ivanikov IO. Novel approach to treatment of refractory peptic ulcers using intranasal Semax. Clinical Gastroenterology. 2002.
- Stavchansky VV, Yuzhakov VV, Sevan'kaeva LE, et al. Melanocortin Derivatives Induced Vascularization and Neuroglial Proliferation in the Rat Brain under Conditions of Cerebral Ischemia. Curr Issues Mol Biol. 2024;46(3):2071–2092.
- Volodina MA, Sebentsova EA, Glazova NY, et al. Semax Attenuates the Influence of Neonatal Maternal Deprivation on the Behavior of Adolescent White Rats. Bull Exp Biol Med. 2012;152(5):560–563.
Related Research Questions
Want the complete research review?
View Full Semax Research Page→FOR RESEARCH USE ONLY
This content is provided for educational and informational purposes only. Products are furnished for in-vitro studies only and are not medicines, drugs, or supplements. Not approved by the FDA to prevent, treat, or cure any condition.