NA-Semax Amidate
N-Acetyl-L-methionyl-L-glutamyl-L-histidyl-L-phenylalanyl-L-prolyl-glycyl-L-prolinamide (Ac-Met-Glu-His-Phe-Pro-Gly-Pro-NH2)
NA-Semax Amidate is a doubly modified (N-acetylated, C-amidated) analog of the Russian neuropeptide Semax (ACTH 4-10 fragment), designed for enhanced metabolic stability. No direct human clinical trials exist for NA-Semax Amidate; mechanistic and efficacy signals are extrapolated from parent Semax literature, including BDNF upregulation (PMID 16635254) and immune/vascular gene modulation in ischemia models (PMID 24661604).
Last updated: 2026-03-09
Safety Summary
Direct NA-Semax Amidate safety data are sparse; all safety information below is derived from parent Semax clinical use in Russia and community reports. According to a review cited in the ADDF cognitive vitality report, the most common adverse events with Semax are nasal cavity discoloration (~10% of patients) and increased blood glucose in diabetics (~7.4% of patients) (Kolomin et al., 2013, review). No consistent reports of severe toxicity, organ damage, or dependence have been published (Swolverine review citing Russian prescribing data). Semax has been used safely in intranasal doses from 600 mcg/day to 12 mg/day for up to 30 days without major side effects (peptides.org review, references [25], [32], [33]). Community reports (online communities, forums) note appetite suppression, vivid dreams, improved mental clarity, and rare hair shedding. Side effects are generally dose-dependent and resolve upon discontinuation. Long-term safety data are limited.
Known Side Effects
common
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Who Should NOT Use This
Allergic reactions possible; compound-class risk that extends to NA-Semax Amidate as an ACTH(4-10) derivative (Russian product leaflet; IntercoastalHealth review).
Insufficient safety data in pregnant or lactating populations. Listed as contraindication in translated Russian Semax product leaflet, but data is for parent compound, not NA-Semax Amidate specifically (IntercoastalHealth review).
Neurostimulatory effects may lower seizure threshold in susceptible individuals. Listed in translated Russian product leaflet for parent Semax (IntercoastalHealth review).
Dopaminergic and neurostimulatory effects may exacerbate psychotic symptoms. Listed in translated Russian Semax product leaflet (IntercoastalHealth review; Patsnap Synapse review).
Semax may have stimulant-like effects leading to increased anxiety in some individuals (ADDF cognitive vitality review; Patsnap Synapse review).
Semax affects dopaminergic and serotonergic systems; combination with drugs influencing these neurotransmitters could amplify effects or cause unpredictable interactions (Patsnap Synapse review). No formal interaction studies exist.
Talk to Your Doctor
Before considering NA-Semax Amidate, discuss it with your healthcare provider. Ask about potential interactions with your current medications, whether it is appropriate for your health conditions, and what monitoring may be needed.
Sources: [1-12]
Evidence Assessment
Evidence tier 5: Animal/in vitro only, no human data for NA-Semax Amidate specifically. Zero clinical trials for NA-Semax Amidate have been registered on ClinicalTrials.gov. Zero peer-reviewed papers testing NA-Semax Amidate in humans were found in the available corpus. All human evidence (Shmonin 2018 meta-analysis of 8 Russian stroke studies, Lebedeva 2018 fMRI pilot n=24, Gusev 2017 stroke study n=110, cognitive enhancement studies in fatigued subjects) is for the parent compound Semax, which is a structurally different molecule (lacking N-acetylation and C-amidation). The parent Semax would rate approximately tier 3-4 on its own merits (multiple small human studies, meta-analysis, Russian clinical approval). Preclinical evidence for Semax is strong: genome-wide transcriptomic analyses (PMID 24661604), proteomic validation (PMID 34201112), multiple animal behavioral studies, and in vitro anti-amyloid work (PMID 35080861). The stability modifications of NA-Semax Amidate have limited published pharmacokinetic data. The 2018 Shmonin meta-analysis recommended a multicenter double-blind study for parent Semax but none has been registered. Tier 5 reflects the specific compound being profiled; the substantial parent Semax evidence base is a strong basis for further research but does not constitute direct human evidence for the analog.
1The peptide semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia: genome-wide transcriptional analysisPMID 24661604
Medvedeva et al. - BMC Genomics (2014) - animal study (genome-wide transcriptional analysis) - Rat model, permanent middle cerebral artery occlusion
Parent Semax altered expression of 96 genes at 3h and 68 genes at 24h after ischemia onset. Only 10 genes overlapped between timepoints. Immune response was most markedly affected: chemokine genes (CCL2, CCL5, CCL7, CCL19, CXCL9, CXCL10, CXCL11), MHC class I/II, immunoglobulin genes upregulated. Vascular system genes affected (angiogenesis, blood vessel stabilization). BDNF mRNA fold change 1.88 at 24h (p=2.0E-04). Calcium regulation genes also modulated.
Limitations: Animal model only (rats). Single ischemia model (pMCAO). Short follow-up timepoints (3h, 24h). Parent Semax tested, not NA-Semax Amidate.
2Semax binds specifically and increases BDNF protein in rat basal forebrainPMID 16635254
Not specified in source data - Not specified in source data (2006) - animal study - Rat model
Parent Semax binds specifically in the basal forebrain and increases BDNF protein levels. BDNF increase observed in basal forebrain but not in cerebellum, suggesting regional selectivity.
Limitations: Animal study only. Regional specificity limits extrapolation to whole-brain effects.
3Neurotrophin gene expression in rat brain under Semax actionPMID 17353092
Not specified in source data - Not specified in source data (2007) - animal study - Rat model
Parent Semax modulates neurotrophin gene expression in rat brain, affecting both BDNF and NGF pathways.
Limitations: Animal study. Parent Semax tested, not NA-Semax Amidate.
4Comparison of NGF and BDNF gene expression under Semax actionPMID 19662538
Not specified in source data - Not specified in source data (2010) - animal study - Rat model
Comparison of NGF and BDNF gene expression patterns under parent Semax administration, demonstrating modulation of both neurotrophic factor systems.
Limitations: Animal study. Parent Semax tested, not NA-Semax Amidate.
5Semax, a Synthetic Regulatory Peptide, Affects Copper-Induced Abeta1-40 Aggregation and Amyloid Formation in Artificial MembranesPMID 35080861
Not specified (PMC8855339 authors) - ACS Chemical Neuroscience (2022) - in vitro biophysical study - In vitro (artificial membrane models)
Parent Semax inhibits copper-induced amyloid-beta (Abeta1-40) fiber formation in absence of model membrane. In presence of Cu2+ ions, Semax sequesters metal ions and inhibits Abeta:Cu2+ complex formation. Also interacts with Abeta:Cu2+ oligomers, retarding formation of protofibrillar and fibrillar species.
Limitations: In vitro study only; no in vivo or clinical validation. Artificial membrane models may not fully replicate biological conditions. Parent Semax tested, not NA-Semax Amidate.
6Semax has high affinity for copper(II) and protective ability against metal toxicityPMID 25310602
Not specified in source data - Not specified in source data (2015) - in vitro - SH-SY5Y neuroblastoma and RBE4 endothelial cell lines
Parent Semax forms stable complexes with copper(II) and prevents copper-induced cytotoxicity on SH-SY5Y neuroblastoma and RBE4 endothelial cell lines.
Limitations: In vitro study only. Cell line models may not reflect in vivo conditions. Parent Semax tested.
7Brain protein expression profile confirms the protective effect of the ACTH(4-7)PGP peptide (Semax) in a rat model of cerebral ischemia-reperfusionPMID 34201112
Sudarkina et al. - International Journal of Molecular Sciences (2021) - animal study (proteomics) - Rat model, cerebral ischemia-reperfusion
Proteomic analysis confirmed the protective effect of parent Semax at the protein expression level in cerebral ischemia-reperfusion model.
Limitations: Animal model only. Proteomic changes may not directly translate to clinical outcomes. Parent Semax tested.
8Novel insights into the protective properties of Semax at the transcriptome levelPMID 32580520
Filippenkov et al. - Not specified in source data (2020) - animal study (transcriptomics) - Rat model
Provided novel insights into parent Semax neuroprotective properties at the transcriptome level, expanding understanding of gene networks affected.
Limitations: Animal model only. Parent Semax tested.
9Semax regulates expression of immune response genes during ischemic brain injuryPMID 28255762
Not specified in source data - Not specified in source data (2017) - animal study - Rat model
Parent Semax regulates expression of immune response genes during ischemic brain injury, supporting its immunomodulatory mechanism.
Limitations: Animal model only. Parent Semax tested.
10Semax targets mu opioid receptor for functional recovery after spinal cord injuryPMID 40692165
Not specified in source data - Not specified in source data (2025) - animal study - Not specified in source data
Identified the mu opioid receptor as a functional target of parent Semax in promoting recovery after spinal cord injury.
Limitations: Recent publication (2025). Full details not available in downloaded papers. Parent Semax tested.
11Attenuation by a novel synthetic analogue of ACTH4-7 of the learning and memory deficits in juvenile rats treated with amphetamine in utero: role of nitric oxide
Bashkatova et al. - BMC Pharmacology (meeting abstract) (2009) - animal study (conference abstract) - Juvenile rats, prenatal amphetamine exposure model
Semax reversed prenatal stress (amphetamine)-induced learning and memory deficits in juvenile rats at 25 days of age. Semax prevented the increase of NO generation and was associated with reduced lipid peroxidation in the hippocampus.
Limitations: Conference meeting abstract only. Animal model only. Limited methodological detail. Parent Semax tested.
12Meta-analysis: Semax effectiveness in the acute period of stroke
Shmonin et al. - Bulletin of Rehabilitation Medicine (Vestnik Vosstanovitelnoi Meditsiny) (2018) - meta-analysis - 8 studies identified (n=654 total); 3 studies (n=181) met strict inclusion criteria for meta-analysis
Intranasal 1% Semax in acute stroke reduced NIHSS scores at days 10-14 for severe and moderate strokes, and at day 21 across all severity subgroups. Rankin scale at day 21: better outcomes for severe and moderate strokes. Rivermead mobility index: significantly better results for Semax across ALL severity subgroups at days 10-14. Authors recommended multicenter double-blind study.
Limitations: Russian-language studies only. Small total sample in analyzed subset (n=181). High heterogeneity (I-squared up to 98% for some subgroups). Studies from Russian centers with varying methodological quality. No ClinicalTrials.gov registration. Parent Semax only, not NA-Semax Amidate.