Semax Nootropic and neuroprotective peptide — A complete scientific guide
Semax, a synthetic analogue of the ACTH(4-10) fragment, is a heptapeptide developed by the Institute of Molecular Genetics in Moscow. It is being studied for its nootropic and neuroprotective properties, and its ability to modulate BDNF expression in the central nervous system.
What is Semax?
Le Semax is a synthetic heptapeptide sequence Met-Glu-His-Phe-Pro-Gly-Pro, derived from fragment 4-10 of adrenocorticotropic hormone (ACTH). The original sequence ACTH(4-10) — Met-Glu-His-Phe-Arg-Trp-Gly — has been modified by the addition of the C-terminal pattern Pro-Gly-Pro (identical to that of Selank) to increase metabolic stability.
Developed in the 1980s, the Semax has been studied in more than 100 publications referenced in PubMed, covering neuroprotection, cognition and neurotrophic modulation.
Documented mechanisms of action
Regulation of BDNF and neurotrophin
The best-documented mechanism of Semax is the positive regulation of the BDNF (Brain-Derived Neurotrophic Factor) and its signaling pathways:
- Increased expression of BDNF mRNA in the hippocampus, frontal cortex, and striatum
- Activation of the TrkB → Ras → ERK/MAPK pathway involved in neuronal survival
- Upregulation of TrkB receptor expression in cortical neurons
- Parallel increase in NGF and NT-3 in certain brain regions
Dopaminergic and serotonergic modulation
Semax significantly modulates central monoaminergic systems:
- Increased turnover of the dopamine in the striatum and the nucleus accumbens
- Modulation of D1 and D2 receptor expression in the prefrontal cortex
- Influence on serotonin metabolism in the hypothalamus and midbrain
- These monoaminergic effects are distinct from those of native ACTH (no effect on the adrenal-cortico-aldosterone axis)
Neuroprotection
Several neuroprotective mechanisms have been documented in vitro and in vivo:
- Reduction of neuronal oxidative stress via upregulation of antioxidant enzymes (SOD, catalase)
- Inhibition of the mitochondrial apoptotic cascade in ischemic neurons
- Modulation of the expression of stress response genes (HSP70, Bcl-2)
- Reduction of neuroglial inflammation via modulation of pro-inflammatory cytokines
Genomic effects
Transcriptomic studies reveal that Semax modulates the expression of more than 90 genes in the rat brain, grouped into functional clusters:
- Neurotrophic genes (BDNF, NGF, NT-3, TrkB)
- Synaptic plasticity genes (Arc, Egr1, c-Fos)
- Genes involved in monoamine metabolism (TH, COMT, MAO)
- Innate immune response genes
Research data
| Model | Result | Dose |
|---|---|---|
| Morris's Water Maze (rat) | Improved spatial memory (+30% vs control) | 50-100 mcg/kg intranasal |
| Focal cerebral ischemia (rat) | Reduction in infarct volume of 25-30% | 100-300 mcg/kg |
| Passive avoidance test (rat) | Improvement in memory retention at 24h and 72h | 50 mcg/kg |
| Neurodegeneration model (mouse) | Protection of dopaminergic neurons in the substantia nigra | 100 mcg/kg |
| Neuronal cultures (in vitro) | Increase in neuronal survival of 40% under oxidative stress | 100 nM |
Pharmacological profile
| Setting | Value |
|---|---|
| Molecular mass | 813.9 Da |
| Main route of administration | Intranasal |
| BHE Passage | Yes (documented by radioactive marking) |
| Metabolic stability | Enhanced by the PGP sequence (vs native ACTH 4-10) |
| Corticotropic effect | Absent (unlike full-length ACTH) |
| Tolerance | No documented tachyphylaxis with chronic administration |
Semax Variants
Several modified analogues of Semax have been developed for research:
- N-Acetyl Semax (NASA) : acetylated version with increased stability and improved BBE penetration
- N-Acetyl Semax Amidate (NASMA) : double modification (N-terminal acetylation + C-terminal amidation) for maximum resistance to aminopeptidases and carboxypeptidases
- Semax + Adamantane : conjugate studied for an extended half-life
The N-Acetyl Semax Amidate (NASMA) version is often preferred in research for its superior stability, although published data are mostly based on unmodified Semax.
Applications in laboratory research
In a scientific research context, Semax is studied for:
- Models of cerebral ischemia and neuroprotection
- Research on synaptic plasticity and memory (BDNF/TrkB)
- Studies of the central dopaminergic system
- Investigation of the genomic effects of peptides on the brain transcriptome
- Models of age-related cognitive decline
- Research on the Semax + Selank combination
Semax certified HPLC 99%+ available
MyPeptide offers the Semax research sample with Janoshik certificate of analysis. Shipping from the European Union in 48-72 hours.
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