Also known as: ACTH(4-10)-Pro-Gly-Pro · Met-Glu-His-Phe-Pro-Gly-Pro
Semax is a synthetic heptapeptide analog of the adrenocorticotropic hormone (ACTH) 4–10 fragment, developed at the Institute of Molecular Genetics of the Russian Academy of Sciences. It is approved in Russia for treating stroke, brain trauma, optic nerve disease, and cognitive disorders, with a strong BDNF-upregulating profile.
Semax was developed in Russia in the 1980s and approved by the Russian Ministry of Health in 1995. It remains one of the few research peptides with a formal approval history, having been granted status for treatment of ischemic stroke, TIA, optic atrophy, and cognitive disorders in Russia and Ukraine.
Unlike ACTH itself, Semax lacks hormonal activity (no adrenal stimulation) because its sequence does not include the corticotropic activity domain. Instead, the Pro-Gly-Pro tripeptide addition from prolyl-endopeptidase cleavage gives Semax its neuroprotective properties and significantly extends its metabolic stability compared to ACTH(4-10). It is most commonly administered intranasally, bypassing the blood-brain barrier effectively.
Semax produces a rapid and sustained 4–8 fold increase in BDNF (Brain-Derived Neurotrophic Factor) mRNA expression in the hippocampus and cortex. BDNF is the primary driver of neuronal survival, synaptogenesis, and long-term potentiation — the molecular substrate of learning and memory formation.
Semax increases dopaminergic and serotonergic tone in the prefrontal cortex and limbic system, contributing to its anxiolytic and pro-cognitive effects. It upregulates DAT (dopamine transporter) expression and modulates 5-HT₂ receptor activity.
Under ischemic conditions, Semax activates HIF-1α (hypoxia-inducible factor), triggering a neuroprotective gene expression cascade that reduces apoptosis, suppresses neuroinflammation (via NF-κB), and promotes angiogenesis in penumbral brain tissue.
Semax is a synthetic heptapeptide derived from the N-terminal fragment of ACTH (residues 4–7), extended with Pro-Gly-Pro to resist enzymatic degradation. It has been approved in Russia for stroke treatment and cognitive enhancement since the 1990s. No significant side effects noted at standard doses; stimulatory effects may cause anxiety at high doses in sensitive individuals. Available as 0.1% and 1% nasal solutions.
Short cycles are standard for Semax to prevent receptor adaptation and maintain consistent cognitive effects. Some researchers use it acutely (7–14 days) for specific tasks or recovery windows rather than continuous supplementation. Stacking with Selank (anxiolytic peptide) is common to balance Semax's stimulatory profile.
Ask anything about Semax — mechanisms, dosing protocols, interactions, or research comparisons.
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