Semax
Human trialACTH(4-7)PGP · Semax acetate · Met-Glu-His-Phe-Pro-Gly-Pro
Highest available evidence among curated papers: Human trial (as of 2026-06-04).
Chemical & identity
- Sequence
- MEHFPGP
- Length
- 7 residues
- Molecular formula
- C37H51N9O10S
- Molecular weight
- 813.9 g/mol · PubChem
- PubChem CID
- 9811102 · PubChem
- SMILES
- CSCC[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)N3CCC[C@H]3C(=O)NCC(=O)N4CCC[C@H]4C(=O)O)N
- InChIKey
- AFEHBIGDWIGTEH-AQRCPPRCSA-N
- Category
- Nootropic/Neuropeptide
Chemical/structural fields are auto-pulled and source-linked.
Mechanism (curated)
Synthetic ACTH(4-10) analog; proposed to modulate BDNF/neurotrophin expression and monoaminergic (dopamine/serotonin) signaling, with copper(II)-chelating activity. Mechanism not fully established.
Pharmacology & handling
- Half-life
- Short — rapidly degraded by serum and brain aminopeptidases; typically given intranasally.
Research
Sudarkina OY et al. · International journal of molecular sciences · 2021 · Animal study
This study evaluated Semax (Met-Glu-His-Phe-Pro-Gly-Pro), a synthetic melanocortin peptide, in a rat transient middle cerebral artery occlusion (tMCAO) model of cerebral ischemia-reperfusion. Brain protein expression profiling at 24 hours post-tMCAO showed that Semax upregulated active CREB in subcortical structures, downregulated MMP-9 and c-Fos in frontoparietal cortex, and downregulated active JNK in both tissues. The authors conclude that suppression of inflammatory and cell death processes alongside activation of recovery mechanisms contribute to Semax's neuroprotective effects at both transcriptome and protein levels. The study used an animal model (rat) with protein expression analysis.
Samotrueva MA et al. · Bulletin of experimental biology and medicine · 2019 · Animal study
This study examined immunocorrecting effects of Semax (Met-Glu-His-Phe-Pro-Gly-Pro) in laboratory animals exposed to "social" stress induced by sensory contact and intermale confrontation. Immune function was evaluated using delayed-type hypersensitivity, agglutination tests, phagocytic activity assays, leukocyte counts, and immunocompetent organ weights. The abstract reports that social stress caused multidirectional changes in immune response, and that Semax restored cellular and humoral immunogenesis reactions and neutrophil phagocytic activity. The authors conclude that Semax has immunomodulating properties warranting further investigation.
Medvedeva EV et al. · BMC genomics · 2014 · Animal study
This genome-wide transcriptional analysis examined how the neuroprotective peptide Semax (Met-Glu-His-Phe-Pro-Gly-Pro) affects gene expression in rat brain cortex tissue following permanent middle cerebral artery occlusion (pMCAO). Semax predominantly enhanced expression of immune-system-related genes, with the effect increasing from 3 to 24 hours post-ischemia; notably, genes encoding immunoglobulins and chemokines showed the greatest changes. The peptide also altered expression of 24 vascular-system genes at 3 hours and 12 genes at 24 hours post-ischemia, affecting processes such as endothelial development, smooth muscle cell migration, and vasculogenesis. The authors conclude that Semax's immunomodulating effects and impact on vascular gene expression are likely key mechanisms underlying its neuroprotective action in focal brain ischemia.
[The efficacy of semax in the tretament of patients at different stages of ischemic stroke].
Human trialGusev EI et al. · Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova · 2018 · Other
A study of 110 patients (43 men, 67 women, mean age 58.0±9.7 years) with ischemic stroke examined semax efficacy at different rehabilitation stages. Patients received semax (6000 mcg/day for 10 days, two courses with 20-day interval) or no semax, divided into early (89±9 days) and late (214±22 days) rehabilitation groups. Semax administration increased plasma BDNF levels regardless of rehabilitation timing, and BDNF increases were associated with improved Barthel index scores and motor performance. The study found positive correlations between BDNF levels and functional recovery, and between early rehabilitation and motor performance improvement.
Eremin KO et al. · Neurochemical research · 2005 · Animal study
This rodent study investigated the effects of Semax, an ACTH(4-10) analogue, on dopaminergic and serotonergic brain systems. Semax administration significantly increased 5-hydroxyindoleacetic acid (5-HIAA), a serotonin metabolite, in the striatum by 25% at 2 hours and up to 180% in extracellular levels within 1-4 hours at 0.15 mg/kg intraperitoneal dose. Semax alone did not alter tissue or extracellular dopamine and its metabolites; however, when administered 20 minutes before D-amphetamine, it dramatically enhanced the effects of D-amphetamine on extracellular dopamine levels and locomotor activity. The results indicate a positive modulatory effect of Semax on the striatal serotonergic system and an ability to enhance dopamine release and locomotor behavior when combined with D-amphetamine.
Dolotov OV et al. · Brain research · 2006 · Animal study
Semax is a heptapeptide analog of ACTH(4-10) that was administered intranasally to rats at 50 microg/kg body weight. In rat hippocampus, Semax increased BDNF protein levels 1.4-fold, trkB tyrosine phosphorylation 1.6-fold, exon III BDNF mRNA 3-fold, and trkB mRNA 2-fold. Semax-treated animals showed increased conditioned avoidance reactions. The authors propose that Semax affects cognitive function through modulation of the hippocampal BDNF/trkB system.
Tomasello MF et al. · Bioinorganic chemistry and applications · 2025 · In-vitro study
Semax (Met-Glu-His-Phe-Pro-Gly-Pro) is a synthetic regulatory peptide tested in vitro for its ability to interact with Cu(II)-amyloid-beta complexes implicated in Alzheimer's disease neurotoxicity. The study found that Semax can extract Cu(II) from Cu(II)-aβ species, inhibit redox cycling of the Cu(II)-aβ complex, and reduce associated reactive oxygen species production. In cell culture (SH-SY5Y cells), Semax demonstrated cytoprotective properties against oxidative stress induced by copper-catalyzed aβ oxidation. The authors propose Semax as a potential therapeutic candidate for neurodegenerative disorders.
Dolotov OV et al. · Journal of neurochemistry · 2006 · Animal study
This animal study examined the mechanism of action of Semax, a heptapeptide analogue of adrenocorticotropin (4-10), in rat basal forebrain. Researchers found that Semax binds specifically to cell membranes isolated from rat basal forebrain in a time-dependent, calcium-dependent, and reversible manner, with a dissociation constant of 2.4±1.0 nM. Intranasal administration of Semax at 50 and 250 µg/kg increased brain-derived neurotrophic factor (BDNF) protein levels in the basal forebrain after 3 hours, but not in the cerebellum. The authors suggest that Semax's cognitive effects may be associated with increased BDNF levels in the basal forebrain.
Gusev EI, Skvortsova VI, Chukanova EI · Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova · 2005 · Other
A study of 187 patients with cerebrovascular insufficiency examined semax treatment using neurological assessment, imaging, and clinical scales. Semax treatment resulted in significant clinical improvement, stabilization of disease progression, and reduced risk of stroke and transient ischemic attacks. The drug showed minor side effects and was well tolerated across age groups, including elderly patients.
Sciacca MFM et al. · ACS chemical neuroscience · 2022 · In-vitro study
This in-vitro study evaluated semax, a synthetic heptapeptide with ACTH-like properties, for its ability to modulate copper-induced amyloid-beta (Aβ) aggregation in artificial membrane models. Researchers used spectrofluorometric, calorimetric, and MTT assays to test whether semax could prevent Aβ:Cu2+ complex formation and inhibit aggregation. The results demonstrated that semax prevented formation of Aβ:Cu2+ complexes and exhibited anti-aggregating and protective properties, particularly in the presence of copper ions, suggesting it inhibits fiber formation by interfering with Aβ:Cu2+ fibrillogenesis.
Miasoedova NF et al. · Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova · 1999 · Other
Semax is a domestic neuropeptide-based nootropic drug that demonstrated angioprotective, antihypoxic, and neurotrophic activity at doses of 100–150 micrograms/kg in experimental studies. A clinical trial in acute ischemic stroke patients combined clinical and electrophysiologic evaluation with immunobiochemical analysis. A retrospective comparative analysis found that Semax activated antiinflammatory postischemic reactions in the brain by shifting the balance of cytokines and inflammatory markers, increasing antiinflammatory agents (interleukin-10, tumor necrosis factor-alpha) relative to pro-inflammatory factors (interleukin-8, C-reactive protein).
Filippenkov IB et al. · Genes · 2020 · Animal study
This study used RNA-Seq analysis to investigate the protective mechanisms of Semax (ACTH(4-7)PGP) in a rat transient middle cerebral artery occlusion (tMCAO) model of cerebral ischaemia-reperfusion. Semax treatment identified 394 differentially expressed genes (>1.5-fold change) in rat brain tissue at 24 hours after tMCAO compared to saline control. The peptide suppressed expression of inflammation-related genes and activated neurotransmission-related genes, whereas ischaemia-reperfusion alone produced the opposite pattern. The authors conclude that Semax's neuroprotective action may involve compensation of mRNA expression patterns disrupted during ischaemia-reperfusion.
Dergunova LV et al. · Molekuliarnaia biologiia · 2021 · Animal study
This animal study (rat model of transient middle cerebral artery occlusion) used qRT-PCR to examine whether Semax suppresses proinflammatory gene expression induced by ischemia-reperfusion injury. Semax exposure led to statistically significant decreases in mRNA levels of Il1a, Il1b, Il6, Ccl3, and Cxcl2. The authors conclude that Semax's protective effect in stroke may be attributable to anti-inflammatory mechanisms, and note limitations of RNA-Seq for quantifying lowly abundant transcripts.
Inozemtseva LS et al. · European journal of pharmacology · 2024 · Animal study
This animal study investigated whether Semax (an ACTH(4-10) synthetic analog) and Melanotan II could produce antidepressant-like effects in male Sprague-Dawley rats exposed to chronic unpredictable stress. Daily intraperitoneal injections of Semax at 60 nmol/kg reversed stress-induced anhedonia, body weight suppression, adrenal hypertrophy, and reduced hippocampal BDNF levels. In the forced swim test, neither the stress procedure nor peptides affected immobility duration. The authors conclude that ACTH(4-10) analogs like Semax may have therapeutic potential for depression in male rats.
Summaries are our own; we link to originals (PubMed / DOI) and never rehost full text.
Regulatory status
- FDA approved
- No
- WADA prohibited
- No
- Compounding status
- Not approved in the US; registered and used clinically in Russia.
- Notes
- Not FDA-approved. Registered/used clinically in Russia for ischemic stroke and cognitive disorders, as of 2026-06-04. Not listed on the WADA prohibited list.
Legal/regulatory status varies by jurisdiction and changes over time — accurate as of last review (2026-06-04).
Data sources: Curated IDs (PubChem/UniProt/ChEMBL) + Europe PMC + ClinicalTrials.gov (2026-06-04).
Last reviewed 2026-06-04