A 7-amino-acid synthetic peptide based on the ACTH (4-10) fragment with an added Pro-Gly-Pro tripeptide for stability. Developed in Russia as a neuroprotective agent for stroke and a cognitive enhancer. Approved in Russia and Ukraine for stroke, TBI, and cognitive disorders.
Semax (Met-Glu-His-Phe-Pro-Gly-Pro) is a synthetic heptapeptide analog of ACTH (4-10), the fragment of adrenocorticotropic hormone responsible for its neurotrophic (but not hormonal) effects. Like Selank, it was developed at the Institute of Molecular Genetics in Moscow and uses the Pro-Gly-Pro C-terminal extension for metabolic stability.
Semax is approved in Russia and Ukraine for treatment of acute ischemic stroke, traumatic brain injury, cognitive disorders, and optic nerve atrophy. It is one of the few peptide drugs approved anywhere for acute stroke treatment. It stimulates BDNF and NGF expression, providing neurotrophic support to damaged neurons.
Semax acts through melanocortin receptors (MC3R and MC4R) in the brain, triggering intracellular cascades that upregulate neurotrophic factor expression. The resulting increase in BDNF and NGF protects neurons from ischemic damage, promotes axonal regeneration, and enhances synaptic plasticity — the cellular basis of learning and memory.
| Pathway | Effect | Significance |
|---|---|---|
| BDNF/NGF upregulation | Increases neurotrophic factor expression via melanocortin signaling | Promotes neuronal survival and regeneration after injury |
| Anti-apoptotic | Activates PI3K/Akt and MAPK survival pathways | Protects neurons from ischemic cell death |
| Neuroplasticity | Enhances synaptic plasticity and long-term potentiation | Improves learning, memory, and cognitive recovery |
| Anti-inflammatory | Reduces pro-inflammatory cytokines in brain tissue | Limits secondary damage after stroke or TBI |
| No hormonal effects | ACTH(4-10) fragment lacks the ACTH(1-3) sequence needed for adrenal stimulation | Neurotrophic benefits without cortisol or aldosterone increase |
| Study | Design | Findings | Level |
|---|---|---|---|
| Acute ischemic stroke | Russian RCTs, n=hundreds | Reduced neurological deficit, improved functional outcomes when given within 6 hours of stroke onset. Basis for Russian approval. | Level I-II (Russian) |
| Traumatic brain injury | Clinical studies | Improved GCS scores and cognitive recovery in TBI patients | Level II |
| Cognitive enhancement | Clinical trials | Improved memory, attention, and information processing in patients with cognitive impairment | Level II |
| Optic nerve atrophy | Clinical studies | Improved visual function in patients with optic nerve damage. Approved indication in Russia. | Level II |
| BDNF increase | Biomarker studies | Measurable increase in serum BDNF levels after intranasal course | Level II-III |
Excellent safety profile: No significant adverse effects in extensive Russian clinical use.
No hormonal effects: Does not stimulate the adrenal glands or affect cortisol/aldosterone levels.
Mild nasal irritation: Occasional nasal mucosal irritation with intranasal administration.
| Jurisdiction | Status |
|---|---|
| Russia/Ukraine | Approved for acute stroke, TBI, cognitive disorders, optic nerve atrophy |
| FDA | Not approved. Not reviewed. |
| Research | Available as a research peptide internationally |