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Neuropeptide · ACTH Derivative

Semax

Met-Glu-His-Phe-Pro-Gly-Pro · ACTH (4-7) Pro-Gly-Pro · Heptapeptide Nootropic

Semax is a synthetic heptapeptide derived from the ACTH(4-10) fragment, with a Pro-Gly-Pro motif added to extend bioactivity to 20–24 hours in animal models. Developed at the Russian Academy of Sciences, it is registered as a medical drug in Russia and Ukraine for stroke, dyscirculatory encephalopathy, and optic nerve atrophy. It represents one of the most clinically advanced synthetic neuropeptides in the world.

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Molecular Profile
SequenceMet-Glu-His-Phe-Pro-Gly-Pro
Length7 Amino Acids
Parent CompoundACTH fragment (4-7)
Serum Half-life>1 hour
Key PathwaysBDNF, dopamine, serotonin
Clinical RegistrationRussia / Ukraine (approved)
NeuroprotectiveBDNF UpregulationNootropicStroke ResearchDopaminergicSerotonergic
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Laboratory Research Compound — For In Vitro Use Only
This compound is supplied by RS Bio Labs solely as a laboratory research material for use by qualified scientific personnel in in vitro research settings. It is NOT approved, intended, or authorised for human consumption, self-administration, diagnostic, therapeutic, or veterinary use of any kind. All research findings referenced on this page are from preclinical models (cell culture, animal studies) unless explicitly stated otherwise. Preclinical data does not establish safety or efficacy in humans. RS Bio Labs makes no medical or health claims.

Neuroprotective Mechanism

Semax's neuroprotective mechanisms have been characterised through multiple complementary approaches. At the cellular level, Semax promotes neuronal survival under hypoxia and glutamate-mediated excitotoxicity — the primary injury mechanisms in ischaemic stroke. It contributes to mitochondrial stability under calcium dysregulation stress and inhibits nitric oxide synthesis, reducing NO-mediated neuronal damage post-ischaemia.

At the transcriptomic level, genome-wide studies of rat brain cortex under focal ischaemia showed Semax predominantly enhanced the expression of immune system genes — over 50% of Semax-modulated genes were immune-response related — alongside 24–36 vascular system genes associated with endothelial migration and vasculogenesis, suggesting an immunomodulatory and pro-vascular mechanism underlying its neuroprotection.

In cognitive research, Semax modulates monoamine neurotransmission — increasing serotonin levels and potentiating dopaminergic compounds in animal models. A single intranasal dose (50 µg/kg) increased BDNF in rat basal forebrain within 3 hours, and in human stroke patients, multi-course treatment elevated plasma BDNF significantly, with high-BDNF patients showing improved rehabilitation timing.

Clinical Use in Stroke

Semax has been used in clinical practice in Russia since the 1990s as an adjunct in stroke management. Human studies in the Russian clinical registry document differences in neurological function scores when added to standard care protocols, and reduced infarction size measurements in photothrombosis models. These are not regulatory-approved findings outside Russia/Ukraine. Multi-course dosing (6,000 µg/day × 10 days) produced significant plasma BDNF elevation compared to controls.

EEG studies in healthy adults demonstrated that Semax (250–1000 µg/kg) produced electroencephalographic changes similar to other established neuroprotective drugs, providing objective physiological evidence of CNS activity in healthy volunteers.

Versus Selank

Semax and Selank are often compared as they were developed concurrently at the Russian Academy of Sciences. Semax is ACTH-derived and is primarily linked to dopaminergic activity and BDNF-related neuroplasticity — making it relevant to research paradigms studying attention, learning, and memory consolidation pathway markers.

Selank, by contrast, is tuftsin-derived and acts mainly through GABAergic and cytokine-modulating pathways — positioning it within studies examining stress signalling, emotional regulatory pathway markers, and anxiolytic mechanisms in preclinical contexts. Their distinct mechanisms make them complementary rather than interchangeable in research contexts.

Key Published Research
Semax Affects Expression of Genes Related to Immune and Vascular Systems in Rat Brain Focal Ischaemia
PMC · 2014 · PMC3987924
Genome-wide transcriptomic analysis following permanent MCAO in rats. Semax modulated >50% of its affected genes via immune response pathways and 24+ vascular system genes at 3h post-ischaemia. Authors concluded immunomodulatory and vascular influence are the key mechanisms underlying neuroprotection in stroke.
Functional Connectomic Assessment of Selank and Semax Effects
PubMed · 2020 · PMID: 32342318
Resting-state fMRI in 52 healthy adults. Semax produced distinct changes in amygdala-temporal cortex functional connectivity versus both placebo and Selank — first neuroimaging characterisation of Semax's acute CNS effects in healthy humans.
Research Context: Semax is registered as a medicine in Russia and Ukraine but is not approved by the FDA or MHRA. Human clinical data is predominantly from Russian-language studies. Available evidence includes stroke therapeutic use, EEG studies in healthy adults, and BDNF elevation data. For scientific reference only.