Semax is a synthetic 7-amino-acid peptide (Met-Glu-His-Phe-Pro-Gly-Pro) derived from a short segment of the hormone ACTH. Unlike ACTH, it does not affect the adrenal glands but acts in the brain: in studies it raised levels of the neurotrophic factor BDNF and protected nerve cells during oxygen deprivation. In Russia it is registered as a medicine in the form of nasal drops; it is not approved in the EU.[1]
Semax at a glance
- Origin: 1980s, Institute of Molecular Genetics of the Russian Academy of Sciences.
- Structure: the ACTH(4–7) fragment extended by the tripeptide Pro-Gly-Pro, which protects it from rapid breakdown.
- Administration: intranasal – the nasal mucosa allows rapid access to the brain.
- Main research areas: BDNF and learning, stroke, attention.
What is Semax and how was it developed?
As early as the 1970s it was known that short segments of the hormone ACTH improve learning and attention in animals, even though they have no hormonal effect on the adrenal glands. The problem was that they break down in the body within minutes. Russian scientists therefore attached the three amino acids Pro-Gly-Pro, which stabilise the peptide, to the ACTH(4–7) segment. The result was Semax, which acts much longer than the original fragment.
How does Semax act on the brain?
BDNF – “fertiliser” for neurons
BDNF (brain-derived neurotrophic factor) is a protein that supports neuron survival, the growth of their connections and learning. In a rat study, a single intranasal dose of Semax raised the levels of BDNF and its TrkB receptor in the hippocampus – the brain region key to memory. The animals also learned faster.[1] Earlier, a Russian team had shown that Semax increases neurotrophin mRNA production in glial cell cultures within tens of minutes.[2]
Dopamine and serotonin
In rodents, Semax activated the brain’s dopamine and serotonin systems, especially in the striatum. This could explain its effect on attention and motivation described in animal studies.[3]
Protection during oxygen deprivation
In a model of stroke in rats, Semax changed the activity of hundreds of genes, mainly those related to the immune response and blood vessels. The authors interpret this as helping the brain cope with damage.[4]
What have studies in humans shown?
Clinical studies come almost exclusively from Russia. The best known followed patients in the acute phase of ischaemic stroke who received intranasal Semax alongside standard treatment. The authors described faster recovery of neurological function.[5] The studies were small and published in Russian journals, however, so Western regulators do not consider them sufficient. Randomised trials to international standards are lacking.
| Area | Model | What was observed |
|---|---|---|
| BDNF and learning | Rats | More BDNF and TrkB in the hippocampus, faster learning[1] |
| Neurotrophins | Glial cells | Rapid rise in neurotrophin mRNA[2] |
| Neurotransmitters | Rodents | Activation of the dopamine and serotonin systems[3] |
| Cerebral ischaemia | Rats | Change in expression of immune and vascular genes[4] |
| Stroke | Patients (Russia) | Faster recovery of function[5] |
Why is Semax given intranasally?
Peptides are broken down in the digestive tract, so tablets make no sense. The nasal mucosa has a rich blood supply, and from the upper nasal cavity there is a route to the brain along the olfactory nerve. Intranasal administration therefore allows Semax to reach the brain quickly and without an injection. That is why in Russia it is sold as 0.1% and 1% nasal drops.
What are the side effects of Semax?
In Russian clinical practice Semax is considered well tolerated. Mild irritation of the nasal mucosa is described, and exceptionally headache or nervousness. However, good long-term safety data are lacking, as are drug interaction studies.
How does Semax differ from Selank?
Both peptides were developed at the same institute and both carry the stabilising tripeptide Pro-Gly-Pro. Semax is based on ACTH and is studied mainly for memory, attention and brain protection. Selank is based on the immune peptide tuftsin and is studied for anxiety and stress.
Why doesn’t Semax have ACTH’s hormonal effects?
The full ACTH hormone has 39 amino acids, and it is its initial part, which binds to the MC2R receptor, that acts on the adrenal glands. Semax contains only segment 4–7 (Met-Glu-His-Phe), which does not activate this receptor. That is why it does not increase cortisol production, yet keeps the effects on the brain that were described for short ACTH fragments as early as the 1970s.
What is N-acetyl Semax amidate?
A modified version of Semax with acetyl and amide end groups, called N-acetyl Semax amidate (NA-Semax-Amidate), also appears on the research peptide market. The modifications are meant to increase stability and duration of action. However, this version has no published peer-reviewed studies comparable to those on the original Semax, and its properties are based more on theory.
How does Semax change gene activity?
Newer Russian work uses whole-transcriptome analysis, i.e. measuring the activity of thousands of genes at once. In a model of cerebral ischaemia, Semax affected mainly genes of the immune response and genes for blood vessel formation and function.[4] The results show that Semax’s effects are not limited to one receptor but reach a wider network of processes that help the brain recover from damage.
How has Semax research developed?
| Period | Event |
|---|---|
| 1970s | Discovery that short ACTH fragments affect learning without hormonal effects |
| 1980s | Synthesis of Semax at the Institute of Molecular Genetics of the Russian Academy of Sciences |
| 1990s | Registration in Russia, clinical studies in stroke[5] |
| 2000–2010 | Studies of neurotrophins and BDNF in animals and cells[1][2] |
| 2010–present | Whole-transcriptome and gene expression analyses[4] |
Semax research is therefore largely a Russian affair. Western pharmaceutical companies have shown no interest in it, and independent studies outside Russia are rare.
Summary
- Semax is a heptapeptide derived from the ACTH(4–7) segment, stabilised by the tripeptide Pro-Gly-Pro.
- It has no hormonal effects on the adrenal glands, but in the brain it increases BDNF and its TrkB receptor.[1]
- In Russia it is registered as nasal drops, mainly for stroke and attention disorders.
- Most studies come from Russia; international randomised trials are lacking, and it is not approved in the EU.
Frequently asked questions
Is Semax a nootropic?
Semax is classed as a nootropic peptide because animal studies describe improved learning and attention. In healthy people, however, good-quality studies have not confirmed these effects.
What is the difference between Semax 0.1% and 1%?
In Russia the lower concentration is used for attention and memory disorders, the higher one for acute stroke. Both forms are nasal drops.
Is Semax approved in the Czech Republic?
No. Semax is not a registered medicine in the Czech Republic or any other EU country; in the Czech Republic it is sold only as a research chemical.
How quickly does Semax act?
In a rat study, BDNF levels in the hippocampus rose within a few hours of a single intranasal dose.[1]
Sources
- Dolotov OV, 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. PubMed ↗
- Shadrina MI, et al. Rapid induction of neurotrophin mRNAs in rat glial cell cultures by Semax, an adrenocorticotropic hormone analog. Neuroscience Letters. 2001;308(2):115–118. PubMed ↗
- Eremin KO, et al. Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents. Neurochemical Research. 2005;30(12):1493–1500. PubMed ↗
- Medvedeva EV, 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. PubMed ↗
- Gusev EI, et al. Effectiveness of semax in acute period of hemispheric ischemic stroke (a clinical and electrophysiological study). Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 1997. PubMed ↗
The information in this article is for educational purposes only and does not replace medical advice. The substances described are not approved medicines, and Jolt Peptides products are intended solely for laboratory research, not for use in humans or animals.