Description

Semax: A Multi-Functional Neuropeptide with Cognitive and Neuroprotective Properties

Semax is a synthetic heptapeptide initially developed in Russia in the 1980s and 1990s that has garnered significant interest for its diverse neurological benefits. This peptide, consisting of a fragment of adrenocorticotropic hormone (ACTH(4-7)) coupled with the C-terminal tripeptide Pro-Gly-Pro, has established itself as an important medication in Russia and Eastern Europe while remaining experimental in Western countries. This report examines Semax’s mechanisms of action, therapeutic applications, and current research status.

Molecular Structure and Origin

Semax (Met-Glu-His-Phe-Pro-Gly-Pro) was developed at the Institute of Molecular Genetics of the Russian Academy of Sciences in Moscow. First described by 1991, this peptide was initially investigated as a treatment for stroke victims suffering brain damage before researchers discovered its significant cognitive enhancement effects in healthy individuals as well^[1].

The peptide is an analog of naturally occurring ACTH hormone, designed to mimic certain beneficial effects while minimizing unwanted side effects. Due to its peptide structure, Semax has poor oral bioavailability and is typically administered parenterally as a nasal spray or subcutaneous injection^[1].

Mechanisms of Action

Semax operates through several complementary neurobiological mechanisms, though its exact mode of action remains incompletely understood.

Neurotrophic Factor Modulation

A primary mechanism involves Semax’s ability to:

·         Rapidly increase levels and expression of brain-derived neurotrophic factor (BDNF) in the hippocampus^[2][3][4]

·         Activate the BDNF/trkB system, with studies showing a 1.4-fold increase in BDNF protein levels and a 1.6-fold increase in trkB tyrosine phosphorylation^[4]

·         Promote a 3-fold increase in exon III BDNF expression^[4]

These effects on BDNF, a protein crucial for neuronal survival and growth, likely contribute significantly to Semax’s cognitive and neuroprotective properties.

Neurotransmitter Regulation

Semax demonstrates significant influence on brain neurochemistry:

·         Rapidly activates serotonergic and dopaminergic brain systems^[1]

·         Modulates the levels of neurotransmitters such as dopamine and serotonin^[2]

·         May act through melanocortin receptors, potentially as an antagonist or partial agonist of MC4 and MC5 receptors^[1]

Gene Expression Modulation

In conditions of brain focal ischemia, Semax has demonstrated remarkable effects on gene expression:

·         Predominantly enhances expression of genes related to the immune system^[5]

·         Influences genes that affect the activity of immune cells, with effects increasing significantly 24 hours after ischemic injury^[5]

·         Modulates expression of genes that encode immunoglobulins and chemokines^[5][4]

·         Affects genes that promote formation and functioning of the vascular system^[5][4]

Anti-Amyloid Properties

Recent research has uncovered Semax’s potential role in Alzheimer’s disease pathology:

·         Forms stable complexes with copper(II) ions^[6][7]

·         Prevents the formation of Aβ:Cu2+ complexes, which are implicated in Alzheimer’s disease^[6][7]

·         Demonstrates anti-aggregating properties against amyloid beta protein, especially in the presence of copper ions^[6][7]

·         Inhibits fiber formation and protects cell membranes from disruption in experimental models^[6][7]

Therapeutic Applications

Semax has been investigated for numerous clinical applications, with varying levels of evidence supporting its efficacy.

Stroke and Circulatory Disorders

·         Used in Russia for prevention and treatment of circulatory disorders including stroke^[4][1]

·         Included on the Russian List of Vital & Essential Drugs^[4][1]

·         A 2018 study with 110 stroke patients reported increases in BDNF levels correlated with early rehabilitation^[1]

Cognitive Enhancement

·         Improves attention, memory, focus, and analytical skills^[3][8]

·         In a 1996 study with 11 healthy subjects, 250-1000 μg Semax improved attention and short-term memory, with effects most pronounced during fatigue^[1]

·         A 2018 study with 24 healthy participants demonstrated increased fMRI default mode network activity compared to placebo^[1]

Neuroprotection

·         Promotes survival of neurons during hypoxia and glutamate neurotoxicity^[5]

·         Contributes to mitochondrial stability under stress induced by calcium ion deregulation^[5]

·         Shows protective effects for diseases of the optic nerve^[5][1]

Potential Applications in Neurological Disorders

Current research suggests potential benefits for:

·         ADHD and attention disorders^[3]

·         Anxiety conditions^[3]

·         Alzheimer’s disease, potentially through its anti-amyloid properties^[6][7]

·         Other neurodegenerative diseases such as ALS and Parkinson’s disease^[3]

Administration and Safety Profile

Semax is typically administered as:

·         A nasal spray for daily or as-needed use^[3]

·         Subcutaneous injections in some applications^[1]

·         Often used in conjunction with Selank, another peptide with complementary effects^[3]

The peptide is generally well-tolerated with minimal side effects. Local injection area complications such as bleeding, infection, or irritation may occur if not administered properly^[3]. It is generally regarded as safer than other cognitive stimulants^[8].

Current Status and Availability

Semax exists in contrasting regulatory environments globally:

·         Approved and widely used in Russia and some Eastern European countries^[1]

·         Listed on the Russian List of Vital & Essential Drugs^[4][1]

·         Not evaluated or approved by the FDA for use in the United States^[2][1]

·         Available primarily as a research compound in Western countries^[1]

Conclusion

Semax represents a promising peptide with multi-faceted neuroprotective, cognitive-enhancing, and potentially disease-modifying properties. Its ability to increase BDNF levels, modulate neurotransmitter systems, regulate gene expression, and potentially interfere with amyloid aggregation suggests applications ranging from everyday cognitive enhancement to serious neurological conditions.

While the peptide has a long history of clinical use in Russia, where it is considered an essential medication, the relative lack of large international clinical trials limits definitive conclusions about its efficacy and safety profile for Western medical applications. As research continues, particularly in areas like Alzheimer’s disease where its anti-amyloid properties show promise, Semax may eventually find broader acceptance in global medicine as a novel approach to neurological health and cognitive function.

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1.       https://en.wikipedia.org/wiki/Semax              

2.      https://synapse.patsnap.com/article/what-is-semax-used-for  

3.      https://www.caseintegrativehealth.com/peptide-therapies/semax       

4.      https://particlepeptides.com/en/content/37-semax       

5.       https://pmc.ncbi.nlm.nih.gov/articles/PMC3987924/      

6.      https://pubs.acs.org/doi/10.1021/acschemneuro.1c00707    

7.       https://pmc.ncbi.nlm.nih.gov/articles/PMC8855339/    

https://particlepeptides.com/en/blog/news/what-is-semax