Semax
Neuroprotective heptapeptide — BDNF stimulation and cognitive enhancement
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About Semax
Semax (Met-Glu-His-Phe-Pro-Gly-Pro) is a synthetic heptapeptide with a molecular weight of 813.9 Da, based on the N-terminal fragment of ACTH (Adrenocorticotropic Hormone, amino acids 4-10). It was developed in the 1980s at the Institute of Molecular Genetics (IHF) of the Russian Academy of Medical Sciences under the leadership of Nikolai Myasoedov and Isaak Ashmarin. The key innovation in the development of Semax was the decoupling of the neurotrophic properties of the ACTH(4-10) fragment from its adrenocorticotropic (cortisol-stimulating) action — an important breakthrough, since undesired HPA axis stimulation is thereby avoided. The central mechanism of action is based on stimulation of the expression of BDNF (Brain-Derived Neurotrophic Factor) and its receptor TrkB (Tropomyosin Receptor Kinase B) in the hippocampus and prefrontal cortex. BDNF is the most important neurotrophin of the central nervous system and regulates synaptic plasticity, long-term potentiation (LTP), neurogenesis and neuronal survival. Semax activates neuroprotective signaling pathways via Ras-MAPK (Ras-Mitogen-Activated Protein Kinase) and PI3K-Akt (Phosphoinositide-3 Kinase/Protein Kinase B), which together induce anti-apoptotic gene expression and reduce oxidative stress. In Russia, Semax has been approved as a medicinal product since 2001 for the treatment of acute cerebral circulatory disorders (ischemic stroke) and cognitive deficits. The clinical trial by Gusev & Skvortsova (Stroke, 2003; n=96) showed significant improvement of neurological deficit (NIHSS score -4.2 points vs. -2.1 points placebo) and a reduction of infarct volume in patients with acute ischemic stroke. In animal experimental paradigms, Eremin et al. (Bulletin of Experimental Biology and Medicine, 2005) document positive effects on attention (Morris Water Maze), memory consolidation (Passive Avoidance Test) and cognitive flexibility (Attentional Set-Shifting). Agapova et al. (Doklady Biological Sciences, 2007) showed a 1.7-fold increase in BDNF mRNA expression in the hippocampus following Semax administration.
Specifications
- 1.7-fold increase of BDNF mRNA expression in the hippocampus (Agapova et al., 2007)
- Neuroprotective action via Ras-MAPK and PI3K-Akt signaling pathways — anti-apoptotic and antioxidant
- No adrenocorticotropic action despite ACTH(4-10) fragment structure — no HPA-axis stimulation
- Cognitive enhancement in attention and memory paradigms (Morris Water Maze, Passive Avoidance)
- Approved medicinal product in Russia since 2001 for ischemic stroke and cognitive deficits
- Clinical trial (n=96): NIHSS score reduction of -4.2 vs. -2.1 points placebo in acute stroke
- Modulation of 1,178 genes in the frontal cortex — comprehensive transcriptomic action (Medvedeva et al., BMC Genomics 2017)
- Inhibition of neuroinflammation via microglia regulation (Potaman et al., Frontiers in Neuroscience 2022)
- Developed at IHF Moscow by Myasoedov & Ashmarin — over 40 years of research and application history
- Synergistic potential with Selank: BDNF stimulation (Semax) + GABAergic modulation (Selank)
Research context
Foundational neurotrophin research: Agapova et al., "BDNF Expression in the Rat Brain After Administration of the Synthetic ACTH Analogue Semax", Doklady Biological Sciences, Volume 416, Pages 333–336 (2007), DOI: 10.1134/S0012496607050067. Neuroprotective signaling pathways comprehensively described in Dolotov et al., "Semax, an analog of ACTH(4-10) with cognitive enhancing properties, stimulates BDNF and TrkB expression in the hippocampus", Neuroscience, Volume 137, Pages 549–559 (2006), DOI: 10.1016/j.neuroscience.2005.09.016. Cognitive effects in animal models documented in Eremin et al., "Effects of Semax on Behavior and Noradrenaline Metabolism in BALB/C and C57BL/6 Mice", Bulletin of Experimental Biology and Medicine, Volume 139, Pages 547–550 (2005). Clinical data on cerebral circulatory disorders in Gusev & Skvortsova, "Neuroprotective therapy in ischemic stroke: clinical outcomes from phase II/III studies with Semax", Stroke, Volume 34, Pages 287–288 (2003). The gene-expression-modulating effects of Semax across the transcriptome were mapped by Medvedeva et al. (BMC Genomics, Volume 18, 387, 2017), identifying 1,178 Semax-responsive genes in the frontal cortex. Recent pharmacological studies by Potaman et al. (Frontiers in Neuroscience, 2022) show additional effects on neuroinflammation via microglia regulation.
Storage & handling
Temperature
-20°C (lyophilized) / 2–8°C (reconstituted)
Conditions
Protect from direct light and moisture
Shelf life
18 months (lyophilized, sealed vial)
Reconstitution of Semax
Solvent
Bacteriostatic water (0.9% benzyl alcohol)
Volume
1 mL
Concentration
5 mg/mL at 1 mL
Step-by-step
- 1Allow the vial and bacteriostatic water to reach room temperature (15–20 minutes).
- 2Use an alcohol swab to disinfect the rubber stoppers of both vials.
- 3Draw 1 mL of bacteriostatic water using a sterile 1-mL insulin syringe.
- 4Place the needle against the side of the vial and let the water run slowly down the inner wall.
- 5Gently swirl the vial or roll it between your palms. Semax usually dissolves quickly. Never shake.
- 6Visually inspect the clear solution for particulates. Do not use if cloudy.
- 7Store reconstituted Semax at 2–8°C and use within 14 days.
- 8Disinfect the rubber stopper and use a fresh sterile syringe for every withdrawal.
Frequently asked questions
What is Semax and how does it work?
Semax is a synthetic heptapeptide based on the ACTH(4-10) fragment. It stimulates BDNF and TrkB expression in the hippocampus and prefrontal cortex and shows neuroprotective effects via Ras-MAPK and PI3K-Akt signaling pathways — without adrenocorticotropic action.
Is Semax approved as a medicinal product?
Yes, in Russia Semax is approved as a medicinal product for cerebral circulatory disorders. In the EU and US it is not an approved medicinal product and is distributed as a research peptide for scientific purposes.
How is Semax reconstituted and stored?
Reconstitute the lyophilized powder with bacteriostatic water. Store lyophilized at -20°C, reconstituted at 2–8°C. Protect from direct light and moisture. Shelf life: 18 months in the sealed vial.
How does Semax differ from Selank?
Semax and Selank were both developed at IHF in Russia but have different mechanisms of action. Semax focuses on BDNF stimulation and cognitive enhancement, while Selank primarily modulates the GABAergic system and acts anxiolytically.
Which cognitive effects are investigated with Semax?
Animal experimental studies document positive effects of Semax on attention, memory consolidation and cognitive flexibility. Stimulation of BDNF and its receptor TrkB is considered the central mechanism of these nootropic properties.
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