Semax is a research compound studied for its role in cognitive & nootropic research. This page covers mechanism of action, published studies, preclinical protocols, and analytical specifications.
Quick Reference: Semax
CAS Number
80714-61-0
Molecular Formula
C37H51N9O10S
Molecular Weight
813.9 g/mol
Sequence / Structure
Met-Glu-His-Phe-Pro-Gly-Pro (ACTH 4-10 fragment with stabilising Pro-Gly-Pro extension)
Physical Form
Lyophilized powder
Purity (QSC)
≥99%
Storage
Store lyophilized at -20°C. Reconstituted: 4°C, use within 14 days. Light-sensitive.
Reconstitution
Add 1–2ml bacteriostatic water or sterile saline per vial. Swirl gently. Protect from UV light.
Mechanism of Action
Semax is a synthetic heptapeptide derived from the adrenocorticotropic hormone (ACTH) 4-10 fragment, with a C-terminal Pro-Gly-Pro extension that dramatically improves metabolic stability. Developed at the Institute of Molecular Genetics of the Russian Academy of Sciences, Semax has drug approval in Russia for cognitive enhancement and neuroprotection in stroke and traumatic brain injury.
BDNF and NGF Upregulation: Semax’s most consistently documented molecular mechanism is upregulation of BDNF (brain-derived neurotrophic factor) and NGF (nerve growth factor) in hippocampal and cortical tissue. Both neurotrophins are essential for synaptic plasticity, neuronal survival, and cognitive function. BDNF upregulation enhances long-term potentiation (LTP) — the cellular correlate of learning and memory. The signalling pathway linking Semax to BDNF expression involves dopaminergic and serotonergic intermediary activity.
Dopaminergic and Serotonergic Modulation: Research has documented Semax’s effects on dopamine turnover in the striatum and prefrontal cortex, and on serotonin metabolite levels in multiple brain regions. These monoaminergic effects are proposed to contribute to cognitive enhancement and antidepressant-like activity observed in rodent models, operating through ACTH receptor-independent pathways.
Neuroprotection Mechanisms: In ischemia and hypoxia models, Semax activates neuroprotective cascades including upregulation of heat shock proteins, anti-apoptotic Bcl-2 family members, and antioxidant enzymes in vulnerable neurons. Research has also documented Semax’s ability to reduce neuroinflammation markers (IL-1β, TNF-α, COX-2) in brain tissue following experimental ischemia.
ACTH Receptor Activity: The parent sequence ACTH(4-10) has weak melanocortin receptor activity (MC2R, MC3R), which contributes to attentional and arousal effects documented in some Semax research. However, the Pro-Gly-Pro extension in Semax reduces this ACTH receptor activity relative to the parent fragment, suggesting its primary CNS effects are largely ACTH receptor-independent.
Research Applications
Neurotrophin Research: Semax is used in BDNF/NGF upregulation studies as a non-toxic stimulus for neurotrophin expression in hippocampal cell cultures and in vivo animal models — an alternative to direct BDNF/NGF protein administration for studies requiring endogenous neurotrophin production.
Stroke and Ischemia Research: Russian clinical data and preclinical studies have examined Semax in focal ischemia models (MCAO), measuring infarct volume reduction, neurological deficit scores, and neuroprotective gene expression as primary endpoints.
Cognitive Enhancement Models: Memory and learning paradigms (Morris water maze, novel object recognition, passive avoidance) are used to characterise Semax’s nootropic claims under baseline conditions and following cognitive impairment induction.
Depression and Anxiety Models: Forced swim test, sucrose preference, and chronic mild stress models examine Semax’s antidepressant and anxiolytic properties — activities linked to its monoaminergic and neurotrophin-modulating mechanisms.
TBI and Neurotoxicity Models: Semax has been studied in traumatic brain injury models and neurotoxin exposure models (glutamate excitotoxicity, 6-OHDA) for neuroprotective activity.
Key Published Research
Primary publications relevant to Semax research. Full citations available via PubMed. QSC does not endorse or make claims based on this research.
Mironova et al. (2007)
“Effects of Semax on the Expression of BDNF and Its TrkB Receptor in Basal Forebrain” — Doklady Biological Sciences
Documents Semax-induced BDNF and TrkB receptor upregulation in basal forebrain — key mechanistic evidence for the neurotrophin hypothesis of Semax’s nootropic activity.
Agapova et al. (2007)
“Semax Attenuates the Effects of Cerebral Ischemia-Reperfusion in Rats” — Bulletin of Experimental Biology and Medicine
Characterises Semax’s neuroprotective effects in a transient focal ischemia model, documenting infarct volume reduction and expression of anti-apoptotic genes.
Eremin et al. (2005)
“Immunostimulatory Effects of Semax” — Bulletin of Experimental Biology and Medicine
Documents Semax’s immunomodulatory activity, suggesting it modulates T-cell function and cytokine production through ACTH receptor-mediated and -independent pathways.
Research Protocol Reference
Model / Context
Dose Range
Route
Protocol Notes
Rodent Cognitive Model
25–250 μg/kg
Intranasal instillation or IP injection
Single-dose or daily for 3–7 days; Morris water maze, NOR test at 24h post-injection
Ischemia Neuroprotection
100–500 μg/kg
IP or intranasal
Administered at ischemia onset or 1h post-MCAO; endpoints: infarct volume (48h MRI), neurological deficit score, BDNF/Bcl-2 Western blot
BDNF Upregulation (in vitro)
1–100 nM
Added to hippocampal neuron culture
24–48h; RT-qPCR and ELISA for BDNF, TrkB phosphorylation, cAMP
Frequently Asked Questions
What is Semax?
Semax is a synthetic heptapeptide derived from ACTH(4-10) with a stabilising Pro-Gly-Pro C-terminal extension. It upregulates BDNF and NGF, modulates dopaminergic and serotonergic neurotransmission, and exerts neuroprotective effects in ischemia models. It has drug approval in Russia for cognitive enhancement and stroke treatment.
What is the difference between Semax and Selank?
Both are Russian-developed nootropic peptides but with different mechanisms. Semax (ACTH-derived) primarily upregulates BDNF/NGF and modulates monoaminergic systems — more cognitive/activating in character. Selank (tuftsin-derived) primarily modulates GABA-A receptors — more anxiolytic in character. They are often studied in combination for complementary effects.
What is NA-Semax Amidate?
NA-Semax Amidate (N-Acetyl Semax Amidate) is a modified form of Semax with N-terminal acetylation and C-terminal amide, designed to improve bioavailability and plasma stability for research requiring longer-lasting CNS activity from a single administration.
How should Semax be stored?
Lyophilized at -20°C, protected from UV light. After reconstitution with bacteriostatic water or saline, store at 4°C and use within 14 days. Semax is more light-sensitive than many peptides — handle away from direct light.
What purity is QSC Semax?
≥99% by HPLC and mass spectrometry. COA on product page, Janoshik-verified.
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