Research Dossier on Semax

(Neuropeptide / Cognitive Enhancer)

Classification & Molecular Identity

Amino acid sequence, molecular weight, structural motifs

• IUPAC name (peptide): Met–Glu–His–Phe–Pro–Gly–Pro (MEHFPGP)—a heptapeptide derived from the adrenocorticotropic hormone (ACTH) core fragment ACTH(4–10). Semax is frequently described as a melanocortin-lineage analog without steroidogenic (pituitary) activity. PubMed

• Nominal mass. Reported analytical masses vary with protonation/salt form; calculations for the free acid typically fall near ~861–875 g·mol⁻¹ (lot/formulation specific; most primary reports emphasize sequence and bioactivity rather than exact mass tables).

• Rationale. The short ACTH(4–10) motif (EHFPG) is preserved within MEHFPGP; the Gly–Pro tail and the His/Phe/Pro core are recurrent in glyproline neuropeptides and have been associated with enhanced stability and CNS activity compared to the parent tetrapeptide in rodent studies. PubMed

Discovery history (lab, year, species)

Semax emerged from Russian peptide-neuroscience programs in the 1990s–2000s as an ACTH(4–10) analog with purported nootropic and neuroprotective actions yet lacking endocrine (adrenal) effects. Early mechanistic and behavioral work in rodents described cognitive enhancement, stress-adaptation, and monoaminergic modulation, followed by gene-expression and proteomic studies that emphasized neurotrophin and immune pathways. PubMed+2PubMed+2

Endogenous vs synthetic origin

• Endogenous: Semax itself is not endogenous. Its ancestor fragment, ACTH(4–10), is embedded within endogenous corticotropin, but Semax is a synthetic derivative purposely designed to retain beneficial CNS actions without endocrine activation. PubMed

• Synthetic production: Solid-phase peptide synthesis; peer-reviewed methods sections report HPLC/MS identity testing for research formulations. PubMed

Homologs, analogs, derivatives

• Tuftsin-lineage analog: Selank (Thr–Lys–Pro–Arg–Pro–Gly–Pro; TKPRPGP)—an anxiolytic-leaning heptapeptide with GABAergic/immune transcriptomic effects; often co-studied with Semax.

• ACTH-lineage variants: Shorter ACTH(4–10) fragments and modified glyproline tails have been explored for stability and signal bias.

• Formulation analogs: Articles frequently reference intranasal (IN) solutions used in experimental medicine and practice settings in Russia; modern, Good-Laboratory-Practice PK-CMC for global dossiers is limited in the indexed English-language literature. PubMed

Historical Development & Research Trajectory

Key milestones

1. Monoamine modulation (2005). In rodent microdialysis, Semax enhanced striatal dopamine release and locomotion after D-amphetamine and modulated serotonergic neurochemistry—an early pointer to monoaminergic crosstalk distinct from benzodiazepines. PubMed

2. Neurotrophin linkage (2003–2006). Semax increased brain-derived neurotrophic factor (BDNF) expression and protein levels in multiple brain areas, including hippocampus and basal forebrain, and altered NGF dynamics on rapid time scales. PubMed+2PubMed+2

3. Ischemic stroke transcriptomics (2014, 2021). In rat focal ischemia, Semax re-programmed genes involved in immune response, chemokine/immunoglobulin signaling, and vascular remodeling—a mechanistic thread echoed in subsequent proteomic studies. BioMed Central+1

4. Intranasal brain access (2006). Using tritium-labeled Semax, investigators detected peptide in rat brain after IN dosing (50 µg·kg⁻¹), supporting nose-to-brain delivery as a plausible route (kinetics characterized in blood and multiple brain regions). Investigational dose used in study Shevchenko 2006. PubMed

5. Human observational/controlled signals (1997–2018). Small clinical series and controlled studies in acute ischemic stroke reported functional and motor improvements and plasma BDNF elevation when Semax was added to early rehabilitation. Methods and reporting quality vary; results should be interpreted with caution. Europe PMC+1

6. Neuroimaging (2018). Acute resting-state fMRI in healthy volunteers showed default-mode networkmodulation within minutes after intranasal Semax vs placebo (exploratory PD without clinical outcomes). PubMed

Paradigm shifts & controversies

• From receptor hunting to network effects. Rather than a single high-affinity receptor, Semax appears to modulate networks tied to neurotrophins (BDNF/NGF), inflammatory/immune genes, and monoamine tone. Whether the peptide engages a specific cell-surface receptor remains Not established; most evidence derives from expression and functional omics. BioMed Central

• Clinical evidence quality. Many human data come from small, regionally published trials without modern CONSORT standards or pharmacokinetic confirmation; efficacy in stroke is suggestive but not definitive by international regulatory criteria. PubMed

Evolution of scientific interest

Interest has widened from nootropic/anxiolytic properties to neuroprotection in ischemia, oxidative stress, and amyloid contexts; recent studies include proteostasis/amyloid fibrillogenesis (e.g., Aβ:Cu²⁺ interactions) and spinal cord injury pathways. PMC+1

Mechanisms of Action

Primary and secondary interactions

• Neurotrophin axis. Multiple studies show that Semax up-regulates Bdnf and Ngf mRNA within 20–90 min in selected regions (e.g., frontal cortex), with time- and region-specific decreases and rebounds, and increases BDNF protein in basal forebrain. These dynamics align with plasticity-relevant effects seen in learning and post-ischemic recovery paradigms. PubMed+2PubMed+2

• Immune/vascular transcriptome re-programming. In rat focal ischemia, Semax enhanced immune-system and chemokine gene cohorts and vascular-system genes (e.g., Cyr61, Atf3, Klf4), consistent with remodeling and repair programs after injury. PMC

• Monoaminergic systems. Microdialysis and biochemical studies indicate Semax modulates dopaminergic and serotonergic parameters and can augment amphetamine-evoked DA release—suggesting neuromodulatorycapacity with potential implications for attention/arousal circuits. PubMed

• Proteostasis/amyloid. In vitro biophysical work indicates Semax interferes with Aβ:Cu²⁺ fibrillogenesis, reducing fiber formation—an anti-aggregation property of potential relevance to synaptotoxic stress. PMC

• Spinal cord & pyroptosis (emerging). Newer preclinical data (SCI mice) implicate lysosomal-membrane–permeabilization (LMP)–linked pyroptosis and USP18/μ-opioid receptor network regulation in Semax-mediated neuroprotection; these findings are early-stage and require independent replication. PubMed

Bottom line. The mechanistic corpus favors multimodal network modulation—not a single orthosteric receptor—including rapid neurotrophin induction, immune/vascular gene programs in ischemia, monoamine crosstalk, and proteostasis effects.

Intracellular signaling pathways (inferred from omics & models)

• BDNF/TrkB-linked plasticity. Repeatedly observed BDNF up-regulation suggests downstream TrkB signaling (e.g., MAPK/ERK, PI3K–AKT), consistent with synaptic plasticity and recovery. Direct TrkB binding by Semax is Not established; effects appear indirect via transcriptional control. PubMed

• Inflammatory/immune cascades. Transcriptomic shifts point to NF-κB-adjacent networks, chemokines, and immunoglobulins, and to vascular remodeling genes after stroke—compatible with post-ischemic immune-vascular coupling. PMC

• Amyloid–metal axis. Interference with Aβ:Cu²⁺ fibril formation fits with metal–peptide interaction paradigms and may reduce ROS-linked aggregate toxicity. PMC

CNS vs peripheral effects

• CNS: Most evidence (neurotrophins, functional connectivity, monoamines) is CNS-focused; intranasaltranslational work supports nose-to-brain access in rodents. PubMed+1

• Peripheral: Immune gene effects in spleen and vascular-system genes in ischemic brain suggest neuro-immune–vascular coupling rather than purely central action. PMC

Hormonal, metabolic, immune interactions

• Semax does not exhibit classic ACTH endocrine activity. Its immune transcriptomic effects and vascularsignatures after ischemia are consistent with repair/inflammation modulation; definitive cytokine-level causal data in humans are Not established.

Evidence grading (A–C)

• A (replicated in vivo/in vitro): BDNF/NGF induction; immune/vascular gene modulation in ischemia; monoamine crosstalk. PubMed+2PMC+2

• B (translational): Default-mode network modulation after IN dosing; functional recovery signals and BDNFincreases in small stroke cohorts. PubMed+1

• C (uncertain/controversial): Primary receptor, complete PK, and large randomized clinical efficacy—Not established.

Pharmacokinetics & Stability

ADME profile

• Absorption/Route. Intranasal (IN) delivery is most frequently reported in human experimental work and regional practice. A tritium-labeled Semax study demonstrated brain penetration and blood kinetics after IN dosing (50 µg·kg⁻¹) in rats. Investigational dose used in study Shevchenko 2006. PubMed

• Distribution. After IN dosing in rodents, Semax was detected in multiple brain regions. In humans, resting-state fMRI changes within 5–20 min of IN dosing (1% solution) provide pharmacodynamic but not PK evidence of CNS engagement. PubMed

• Metabolism & Excretion. Like many short peptides, Semax is likely subject to peptidase degradation (aminopeptidases, endopeptidases). Specific human metabolite maps are Unknown.

• Elimination half-life. Quantitative t½ in humans has not been established in indexed peer-reviewed PK studies. General IN-to-brain reviews emphasize rapid delivery and short systemic residence for small peptides, but Selank/Semax-specific PK remains Not established. PubMed+1

Stability in vitro & in vivo

• In vitro: Stable over short assay windows typical for gene-expression and neurochemical experiments.

• In vivo: Functional effects (BDNF induction, behavior, fMRI) arise quickly after dosing, compatible with short-acting signal triggers rather than sustained systemic exposure.

Storage/reconstitution considerations

Peer-reviewed literature does not provide standardized CMC data for research vials; COA-based stability/storage from the supplier should be followed.

Preclinical Evidence

Neurotrophin induction and regional dynamics

• Rapid gene changes (minutes-hours). Rodent studies show Bdnf/Ngf mRNA changes within 20–90 min after Semax; frontal cortex increases are prominent, while hippocampus/retina exhibit biphasic decreases and rebounds—reflecting region-specific regulation. PubMed+1

• Protein increases. In rat basal forebrain, Semax increased BDNF protein following repeated administration, consistent with a neurotrophic mechanism for cognitive/memory effects. PubMed

Immune/vascular re-programming after ischemia

• Transcriptome (BMC Genomics 2014). After permanent MCA occlusion, Semax increased immune/chemokineand immunoglobulin gene expression and vascular genes (e.g., Cyr61, Atf3, Klf4), at 3–24 h post-ischemia—supporting roles in remodeling and cell trafficking. BioMed Central+1

• Proteome confirmation (2021). A mass-spectrometry–based brain protein profile in ischemic rats corroborated immune and neurotrophic pathway modulation by Semax. PubMed

Monoamine and behavioral pharmacology

• Striatal DA/5-HT. Semax augmented amphetamine-evoked dopamine release and influenced serotonergicindices, consistent with arousal/attention effects; chronic Semax reduced anxiety/depression-like behaviors in rats. Investigational doses used in study: typically 0.05–0.3 mg·kg⁻¹ i.p./IN in rodents; see individual methods.PubMed+1

Oxidative stress and amyloid

• Aβ:Cu²⁺ fibrillogenesis. Semax inhibited amyloid fiber formation in vitro by interfering with Aβ–Cu²⁺ complexes—linking peptide–metal interactions to aggregate control. PMC

Emerging SCI mechanisms

• Spinal cord injury (2025). Semax improved functional recovery and reduced pyroptosis markers via USP18regulation in SCI mice; docking/network analyses nominated the μ-opioid receptor as a potential target(hypothesis-generating; requires replication). PubMed

Dose ranges tested (all investigational)

• Rodent IN dosing in penetration study: 50 µg·kg⁻¹ single dose; brain and blood radioactivity time-courses quantified. Investigational dose used in study Shevchenko 2006. PubMed

• Rodent behavioral: 0.05–0.3 mg·kg⁻¹ (i.p. or IN) across anxiety/learning models (study-specific). PubMed

• Ischemia omics: doses chosen to model neuroprotection in MCAO paradigms; timing typically pre- or post-insult (hours). BioMed Central

Comparative efficacy/safety

• Efficacy: Convergent neurotrophin and immune/vascular signatures with behavioral and learning benefits in rodent ischemia/stress models.

• Safety: Rodent work does not report heavy sedation or myorelaxation typical of benzodiazepines; nonetheless, human long-term safety is Not established.

Limitations

• Exposure verification (PK) rarely accompanies PD readouts.

• Species/strain and paradigm heterogeneity complicate quantitative meta-analysis.

• Primary pharmacological target remains uncertain.

Human Clinical Evidence

Stroke and cerebrovascular contexts

• Hemispheric ischemic stroke (1997; n=30). A prospective study in acute ischemic stroke reported improved neurological scores with Semax vs standard therapy; methods reflect 1990s regional practice and lack modern CONSORT detail (small sample; limited blinding). Investigational regimen used in study Gusev 1997. Europe PMC

• Early rehabilitation (2018; n≈100 per arm). In an open-label or lightly controlled setting, Semax added to early rehab was associated with higher plasma BDNF, faster functional recovery, and better motor outcomes vs usual care. Methodological limitations (allocation/blinding) apply. Investigational regimen used in study Gusev 2018.PubMed

• Reviews summarizing trials. A 2023 peer-reviewed review of neuroprotective peptides cites Semax clinical use in acute ischemic stroke, referencing earlier CNS Drugs summaries; it emphasizes positive clinical observations yet acknowledges unresolved mechanisms and need for modern randomized trials. PMC

Cognitive/attention and experimental medicine

• Resting-state fMRI (2018; healthy volunteers). Single-session IN Semax (1%) altered default-mode networktopology within 5–20 min vs placebo (n=24); the study assessed brain network PD rather than clinical endpoints. Investigational exposure used in study Lebedeva 2018. PubMed

ADHD/Rett—hypothesis paper

• A 2007 commentary in Medical Hypotheses argued Semax could be explored for ADHD and Rett syndromebased on monoaminergic/BDNF links; this is not clinical evidence. PubMed

ClinicalTrials.gov

• No large, modern randomized, placebo-controlled Semax trials with posted results are indexed in ClinicalTrials.gov as of this writing; regional trials may not be registered internationally. Status: Not established.

Safety signals/adverse events

• Small clinical series report good short-term tolerability; systematic adverse-event capture, pharmacokinetic confirmation, and long-term safety are insufficiently characterized in the indexed literature. Status:Unknown/Not established.

Comparative Context

Related peptides/approaches

• Selank (TKPRPGP): ACTH-unrelated, tuftsin-derived heptapeptide with GABAergic network effects; both peptides alter gene expression acutely and have been used intranasally in Russian practice/literature.

• BDNF-targeted strategies: Small molecules or activity-based interventions that up-regulate BDNF/TrkB share mechanistic overlap with Semax’s neurotrophin induction.

• Ischemia neuroprotectants: The historical failure rate of neuroprotectants in global stroke RCTs underscores the need for rigorous trial designs before clinical conclusions.

Advantages (research perspective)

• Rapid neurotrophin induction (BDNF/NGF);

• Immune/vascular transcriptomic remodeling post-ischemia;

• Monoamine modulation with non-sedating behavioral profiles in rodents;

• Intranasal brain access demonstrated in animals with PD correlates in humans. PubMed+1

Disadvantages/constraints

• Primary target unknown;

• Human PK and dose–exposure relationships Not established;

• Clinical evidence consists mostly of small, regionally published studies without large, blinded RCTs.

Research category placement

Semax is best positioned as a research tool for studying neurotrophin-driven plasticity, neuro-immune–vascularcrosstalk in ischemia, monoaminergic modulation, and intranasal CNS delivery paradigms.

Research Highlights

• Neurotrophin signature. Semax up-regulates BDNF/NGF genes within an hour and increases BDNF proteinregionally—consistent with plasticity and recovery phenotypes. PubMed+1

• Immune-vascular re-programming in stroke. Omics show Semax enhances immune/chemokine and vasculargenes early after ischemia; proteomics confirms pathway shifts. PMC+1

• Monoaminergic augmentation. Positive modulation of DA/5-HT systems and potentiation of amphetamine-evoked DA release in rodents. PubMed

• Intranasal brain access & PD. Tritium-labeled Semax reaches the rat brain after IN dosing; rs-fMRI in humans supports fast CNS PD. PubMed+1

• Ischemia and beyond. Signals in stroke cohorts (functional recovery; plasma BDNF), Aβ:Cu²⁺ fibrillogenesis inhibition, and SCI pyroptosis pathways broaden the investigative scope. PubMed+2PMC+2

Conflicting/uncertain areas

• Definitive receptor and human PK remain unresolved;

• Clinical effectiveness needs large, blinded trials;

• Translational generalizability outside regional practice contexts is Unknown.

Potential Research Applications (no clinical claims; research-use framing)

1. Neurotrophin-centric plasticity programs

   • Map time-resolved BDNF/TrkB signaling (p-TrkB, ERK, AKT) after Semax, with chromatin assays (ChIP-seq for activity-dependent transcription factors) to understand rapid gene-regulatory triggers. PubMed

2. Stroke immuno-vascular remodeling

   • Combine single-cell RNA-seq and spatial proteomics in MCAO models ± Semax to dissect chemokine, immunoglobulin, and angiogenic modules implicated by transcriptomics. PMC

3. Monoamine network integration

   • Using fiber photometry and microdialysis, quantify DA/5-HT dynamics in behaving animals under attentional load; contrast with BDNF-dependent synaptic markers to integrate arousal and plasticity axes. PubMed

4. Amyloid–metal homeostasis

   • Validate Semax effects on Aβ–metal (Cu²⁺/Zn²⁺) assembly in neuronal co-cultures and organotypic slices, tracking ROS, synaptotoxicity, and long-term potentiation. PMC

5. Intranasal translational PK–PD

   • Establish LC–MS/MS-based Semax PK in rodents/large animals after IN and parenteral dosing; calculate direct transport percentage (DTP) and brain:plasma ratios; pair with EEG/fMRI to relate exposure to network PD. PubMed+1

6. Early-phase human experimental medicine

   • In healthy volunteers or low-risk cohorts, combine single-dose IN Semax with rs-fMRI, MRS (Glx/GABA), and cognitive batteries (attention/executive tasks) to build exposure-response models and identify biomarkers for future RCTs. PubMed

Safety & Toxicology

Preclinical

Across rodent studies, Semax is generally well tolerated at investigational doses (often 0.05–0.3 mg·kg⁻¹, acute or short courses). Studies do not report benzodiazepine-like sedation or myorelaxation, aligning with a non-GABA_A-orthosteric profile. Long-term GLP toxicology (repeat-dose, reproductive, carcinogenicity) specific to Semax is notcomprehensively published in indexed journals. Status: Not established.

Human

Small regional clinical studies and experimental imaging report good short-term tolerability; however, systematic AE capture, pharmacokinetic exposure verification, and long-term safety outcomes are insufficient to define risk. Status:Unknown/Not established.

Specific concerns to monitor in future work

• Immunogenicity of repeated peptide dosing (low likelihood for short peptides but requires data);

• Off-target monoaminergic effects at higher exposures (given DA/5-HT modulation);

• Nasal mucosal tolerability under chronic IN use;

• Drug–drug interactions with psychostimulants or antidepressants (hypothesis-generating from rodent DA/5-HT data).

Limitations & Controversies

• PK knowledge gap. Lack of human Semax PK fundamentally limits dose-exposure-response modeling. PubMed

• Mechanistic ambiguity. While BDNF/NGF and immune/vascular effects are consistent, a single primary targethas not been identified; newer SCI data proposing μ-opioid receptor involvement are preliminary. PubMed

• Evidence concentration. Much of the clinical literature is regional (Russia/Eastern Europe) with heterogeneoustrial designs; independent multicenter randomized evidence is lacking. PubMed

• Translatability risk. Decades of negative RCTs for neuroprotectants in global stroke trials emphasize the need for robust designs before inferring real-world benefit.

Future Directions

1. Foundational human PK. Perform dose-escalation studies (IN ± parenteral) with quantitative LC–MS/MS, nasal deposition imaging, and population PK to define bioavailability, t½, and brain exposure surrogates.

2. Mechanism deconvolution. Use CRISPR perturbations of TrkB and immune-pathway nodes in MCAO models; deploy phospho-proteomics to connect BDNF induction to downstream effectors.

3. Randomized stroke RCTs. Design placebo-controlled, blinded trials in acute ischemic stroke with early administration, standard-of-care background, and core-lab imaging; incorporate plasma BDNF, proteomicbiomarkers, and functional endpoints (mRS, NIHSS).

4. Cognitive/attention indications. Test Semax in attention/arousal tasks (e.g., ADHD-adjacent experimental paradigms) with fMRI/EEG biomarkers and crossover designs, informed by monoaminergic data. PubMed

5. Proteostasis angle. Extend Aβ:Cu²⁺ findings to in vivo AD models (e.g., 5xFAD) to assess synaptic and behavioral rescue under well-controlled exposure.

References

1. Dolotov OV, et al. The heptapeptide SEMAX stimulates BDNF expression in different areas of the rat brain in vivo.Dokl Biol Sci. 2003;391:292–295. PMID: 14556513. PubMed

2. Dolotov OV, et al. Semax… increases levels of BDNF protein in rat basal forebrain. J Neurochem.2006;97(S1):82–86. PMID: 16635254. PubMed

3. Eremin KO, et al. Semax… cognitive effects and monoamine systems. Bull Exp Biol Med. 2005;140: (PubMed: 16362768). PubMed

4. Agapova TI, et al. Semax and temporal dynamics of Bdnf/Ngf expression. Ross Fiziol Zh. 2008;94: (PMID: 18756821). PubMed

5. Shadrina M, et al. NGF and BDNF mRNA after Semax in rat brain/retina. Dokl Biol Sci. 2010;434: (PMID: 19662538). PubMed

6. Medvedeva EV, et al. Semax affects expression of genes related to immune/vascular systems after MCAO. BMC Genomics. 2014;15:228. PMID: 24625048; PMCID: PMC3987924. BioMed Central

7. Sudarkina OY, et al. Brain protein expression profile confirms protective properties of Semax in ischemia. Int J Mol Sci. 2021;22(12):6179. PMID: 34201112. PubMed

8. Shevchenko KV, et al. Kinetics of Semax penetration into brain and blood after intranasal administration. Bull Exp Biol Med. 2006;141: (PMID: 16523722). PubMed

9. Lebedeva IS, et al. Effects of Semax on the default-mode network (rs-fMRI). Bull Exp Biol Med. 2018;165(4): (PMID: 30225715). PubMed

10. Gusev EI, et al. The efficacy of Semax in treatment of patients at different stages of ischemic stroke. Zh Nevrol Psikhiatr Im S S Korsakova. 2018;118(5): (PMID: 29798983). PubMed

11. Gusev EI, et al. Effectiveness of Semax in acute period of hemispheric ischemic stroke. Zh Nevrol Psikhiatr Im S S Korsakova. 1997;97(9): (PMID: 11517472). Europe PMC

12. Dergunova LV, et al. Neuroprotective peptides & strategies for ischemic stroke. Int J Mol Sci. 2023;24: (PMCID: PMC10218113). PMC

13. Sciacca MFM, et al. Semax affects Aβ:Cu²⁺ fibrillogenesis. Int J Mol Sci. 2022;23(6): (PMCID: PMC8855339). PMC

14. Tsai S-J. Semax as potential ADHD/Rett therapy (hypothesis). Med Hypotheses. 2007;68:1144–1146. PMID: 16996699. PubMed

15. Erdő F, et al. Evaluation of intranasal delivery to the brain. Brain Res Bull. 2018;143: (PMID: 30449731). PubMed

16. Maeng HJ, et al. IN PK/PD—solid lipid nanoparticles & nose-to-brain overview. Pharmaceutics. 2022;14: (PMID: 35335948). PubMed

17. Glazova NY, et al. Semax attenuates long-term SSRI exposure effects (rodents). Bull Exp Biol Med. 2021;170: (PMID: 33418449). PubMed

18. Panikratova YR, et al. Acute IN peptide effects on brain networks (Semax & Semax-related). Bull Exp Biol Med.2018; (PMID: 30225715). PubMed

19. Filippenkov IB, et al. ACTH(4–7)PGP (Semax) transcriptome & protective properties (review). Genes.2020;11(6):681. (DOI available). MDPI

20. Sebentsova EA, et al. Long-lasting behavioral effects of neonatal Semax. Ross Fiziol Zh. 2005;91: (PMID: 15835535). PubMed

Representative investigational amounts from the literature
• Intranasal brain-penetration study (rat): 50 µg·kg⁻¹ IN, single dose; time-courses in blood and multiple brain regions (Shevchenko 2006). PubMed
• Behavioral (rodent): 0.05–0.3 mg·kg⁻¹ (i.p. or IN), single or short-course regimens across anxiety/learning models (e.g., Vilenskiĭ 2007). PubMed
• Stroke transcriptomics (rat MCAO): peri-/post-insult dosing protocols specified per study; Semax altered immune/vascular gene cohorts (Medvedeva 2014). BioMed Central
• Human rs-fMRI (healthy volunteers): single 1% IN dose; scans at 5 and 20 min post-dose vs placebo (Lebedeva 2018). PubMed
• Clinical stroke series: regimen per protocol; improvements in BDNF and functional measures reported in small cohorts (Gusev 1997, 2018). Europe PMC+1

⚠️ Disclaimer This peptide is intended strictly for laboratory research use. It is not FDA-approved or authorized for human use, consumption, or therapeutic application.