Semax is a synthetic seven-amino-acid peptide studied for brain responses to injury and for changes in neural signaling. Russian clinical reports describe recovery after ischemic stroke, while animal experiments examine neurotrophins and injury-related gene expression. Small healthy-volunteer studies add observations about resting brain networks. Its literature is useful for tracing how a short ACTH-related sequence affects signaling proteins, tissue responses and measured neurological outcomes under different conditions. Gusev and colleagues (1997), Dolotov and colleagues (2006).
Overview
Molecular profile
Forms and derivatives
ACTH(4–7)-PGP / ACTH(4–10) analogue
Research descriptions referring to Semax's MEHFPGP sequence: the first names the retained ACTH segment and PGP extension; the second names its design relationship to an ACTH fragment.
Semax acetate
An acetate salt of the parent peptide. FDA's review assesses free base and acetate separately and notes inconsistent form identification in clinical reports.
Ac-Semax / N-acetyl Semax / NA-Semax
N-terminally acetylated Semax examined in a 2016 primary chemistry and cell study. Acetylation changed copper coordination and abolished the parent's protection against copper toxicity in SH-SY5Y cells.
NA-Semax Amidate / N-acetyl Semax amidate
The stated name ordinarily denotes N-terminal acetylation plus C-terminal amidation of the Semax sequence.
The Semax sequence is Met-Glu-His-Phe-Pro-Gly-Pro, abbreviated MEHFPGP. Met-Glu-His-Phe corresponds to residues 4–7 of adrenocorticotropic hormone, or ACTH; Pro-Gly-Pro forms the extension. Papers consequently use ACTH(4–7)-PGP and an ACTH(4–10) analogue as descriptions of this heptapeptide. The analogue wording describes its design relationship to an ACTH fragment. The full sequence is the most reliable way to recognize which material a paper studied. Dolotov and colleagues (2006), Medvedeva and colleagues (2017).
Clinical papers often identify the treatment simply as Semax. FDA's 2026 review notes that those reports do not consistently specify whether the material was a free base or acetate salt. This matters when comparing a characterized experimental peptide with a particular formulation. The molecular fields on this page label the parent free-base sequence. FDA Semax briefing document.
Ac-Semax and other terminally modified names
N-acetyl Semax, also written Ac-Semax or NA-Semax, denotes acetylation of the amino terminus. Magrì and colleagues directly examined Ac-Semax in metal-binding and cell experiments. Acetylation changed copper coordination and removed the protection against copper-induced toxicity observed with parent Semax in SH-SY5Y cells. The result shows that a terminal modification can change a measured biological property. Its scope is the tested chemistry and cell assay. Magri and colleagues (2016).
NA-Semax Amidate ordinarily denotes an N-acetylated sequence whose carboxyl terminus is also amidated. The acetylation paper does not establish the properties of this doubly modified material. No direct comparative human clinical or pharmacokinetic study of the amidated derivative was identified in this review. Claims about longer action or better brain delivery need a characterized material and actual exposure measurements.
Uses and research areas
Ischemic stroke occurs when blood supply to part of the brain is interrupted. Researchers have studied Semax in both acute stroke care and subsequent rehabilitation. These settings have different goals: early studies ask about the regression of neurological deficits, while rehabilitation studies ask about motor recovery and the ability to carry out daily activities. Gusev and colleagues (1997), Gusev and colleagues (2018).
Animal work studies cellular responses to reduced blood flow, including inflammation-related signaling and changes in the instructions cells use to make proteins. Healthy-volunteer imaging asks whether an acute exposure changes coordinated brain activity. These experiments help identify plausible biological effects and useful outcomes for later trials. Evidence for general cognitive improvement would require a clinical study that directly measures cognition with appropriate controls and follow-up. Medvedeva and colleagues (2014), Lebedeva and colleagues (2018).
Mechanism of action
One mechanistic theme concerns brain-derived neurotrophic factor, or BDNF. This signaling protein supports several aspects of neuronal function and acts through the TrkB receptor. Dolotov and colleagues measured increases in BDNF protein and TrkB phosphorylation in the rat hippocampus after Semax. Phosphorylation is a chemical change used by cells to switch signaling proteins between activity states. Semax-treated rats made more conditioned avoidance reactions in a learning task. The accessible abstract does not give the task’s full procedure or control preparation. These observations connect a molecular response with behavior in that model; the study's design does not establish that every behavioral effect was caused by the BDNF change. Dolotov and colleagues (2006).
A second theme concerns how injured brain tissue responds at the level of gene expression. A transcriptome is the collection of RNA messages present in a sample. Comparing it across treated and untreated animals can reveal which cellular processes are responding. After permanent focal ischemia, investigators found changes involving immune and vascular systems. A later reperfusion model emphasized suppression of inflammation-related expression and activation of neurotransmission-related expression. Tissue damage, restoration of blood flow and sampling time all influence those patterns. Medvedeva and colleagues (2014), Filippenkov and colleagues (2020).
Semax's Pro-Gly-Pro segment also deserves experimental attention. Comparing intact Semax with that smaller peptide helps test which responses depend on the full sequence. The 2017 transcriptome study reported distinct immune-related expression responses. A fragment therefore cannot automatically carry the complete biological interpretation of its parent peptide. Medvedeva and colleagues (2017).
Pharmacokinetics
Semax's published distribution studies used tritium-labeled peptide in rats after intravenous or intranasal administration. FDA's 2026 evaluation describes greater brain-associated exposure in the intranasal experiments, alongside rapid breakdown in blood and brain tissue. Those results make route and molecular separation important parts of interpreting delivery. The same evaluation found no human pharmacokinetic study of Semax free base or acetate by any route. FDA (2026), pharmacokinetic assessment.
Biodegradation studies provide a complementary picture. Zolotarev and colleagues identified HFPGP and PGP as major products when Semax was exposed to nerve cells. The intact peptide and its fragments can therefore contribute different parts of a time-dependent signal. Measuring each species can connect its presence with the onset and persistence of a biological response. Brain-network and gene-expression measurements describe that response; exposure measurements follow the peptide itself. Zolotarev and colleagues (2006).
Research findings
Acute stroke and rehabilitation reports
The 1997 report by Gusev and colleagues studied 30 patients given Semax during acute ischemic stroke affecting a cerebral hemisphere and 80 patients given conventional treatment. The groups were described as similar in stroke severity and lesion location. Investigators assessed neurological symptoms and electrical activity. Problems with movement and other neurological deficits improved faster when Semax was added to intensive therapy. The indexed abstract does not establish random allocation or blinded assessment and supplies too little numerical outcome information to estimate the size or uncertainty of that advantage reliably. Gusev and colleagues (1997).
The 2018 rehabilitation paper followed 110 patients divided into early and late rehabilitation groups, each subdivided by Semax exposure. The investigators measured plasma BDNF, motor performance and Barthel scores, which reflect assistance needed for everyday activities. They reported higher BDNF and improved Barthel recovery in exposed subgroups; rehabilitation timing also correlated with recovery. Allocation methods and complete numerical uncertainty were unavailable in the accessed abstract. The comparisons therefore need to be interpreted with the timing and surrounding rehabilitation care in view. Gusev and colleagues (2018).
Resting-state imaging in healthy adults
Lebedeva and colleagues studied 24 healthy adults: 14 received an intranasal Semax formulation and 10 received placebo. They obtained resting-state functional MRI scans before exposure and five and twenty minutes afterward. The scans measure coordinated brain activity while a person rests. A medial-frontal part of the default-mode network, a set of regions with coordinated resting activity, occupied a larger scan-defined volume in the Semax group. This measurement concerns which tissue the scan classified as part of the network; it does not mean that brain tissue grew. The experiment did not demonstrate improved memory or attention on a task testing those abilities. Lebedeva and colleagues (2018).
A 2020 report examined connectivity after Semax, Selank or placebo in 52 healthy participants and found differences involving the right amygdala and temporal cortex. The accessible records do not resolve whether participants overlapped with the earlier imaging sample, so these publications should not be added together as independent clinical efficacy cohorts. The translated abstract's administration wording also needs the full method before its route can be assigned confidently. Panikratova and colleagues (2020).
Injury models reveal different molecular responses
In rats with permanently restricted blood supply to part of the brain, the 2014 genome-wide analysis compared Semax-treated animals with animals with the same injury. Semax mainly increased the activity of immune-related genes, including genes encoding chemokines and immunoglobulins; vascular-related genes also changed. The 2017 comparison with PGP further identified a prominent immune-response component, including enhanced antigen-presentation and interferon-related signaling. These findings describe active tissue responses and do not support one uniform direction for every inflammatory process. Medvedeva and colleagues (2014), Medvedeva and colleagues (2017).
Filippenkov and colleagues temporarily blocked an artery in rats, restored blood flow and examined brain tissue 24 hours after the injury. With Semax, RNA messages associated with inflammation were reduced and those associated with communication between nerve cells were increased. Restoring blood flow changes the conditions in injured tissue, which helps explain why these findings differ from experiments in which the artery remained blocked. RNA measurements show how cells respond; tissue examination and tests of recovery are needed to establish what those responses accomplish. Filippenkov and colleagues (2020).
Safety and tolerability
Semax is a registered nasal-drop medicine in Russia, according to FDA's 2026 review; it has no FDA-approved therapeutic indication. The review found insufficient clinical information to characterize safety and no safety data for the proposed subcutaneous route. Its discussion also raises a possible bleeding concern from reported antithrombotic activity. The available material does not provide a reliable rate for that harm. FDA clinical-safety assessment.
FDA's current compounding-risk record separately identifies potential immune reactions associated with aggregation and peptide impurities. Safety depends on the actual formulation, composition and route, as well as the patient's other exposures. The clinical abstracts reviewed here do not provide complete adverse-event tables or sufficiently long follow-up to establish uncommon or delayed effects. FDA compounding-risk record.
What the research means
Semax's experimental literature provides several plausible biological responses: altered neurotrophin signaling, changes in injury-associated transcription, and acute brain-network differences. The clinical reports supply preliminary observations in stroke care and rehabilitation. Establishing a reproducible treatment advantage requires those observations to survive well-reported, controlled comparisons using functional outcomes and comprehensive safety assessment.
The derivative evidence makes chemical identity especially consequential. A measured protective effect changed after N-terminal acetylation in a cell study. That finding is a concrete reason to examine each modified structure on its own terms. It gives no ranking of products for human cognition or stroke recovery.
FAQs
Why do papers use two different ACTH descriptions?
ACTH(4–7)-PGP describes the retained ACTH-related residues followed by the PGP extension. ACTH(4–10) analogue describes the fragment used as a design reference. Both can identify MEHFPGP when the sequence is specified. Dolotov and colleagues (2006).
Does a higher BDNF measurement demonstrate restored brain tissue?
BDNF is a signaling protein. A rise describes a molecular response; tissue structure and functional recovery supply additional information about what that response accomplishes. The cited hippocampal experiment measured rat molecular responses and a conditioning task. Dolotov and colleagues (2006).
What did the healthy-volunteer brain scans measure?
The scans examined which brain regions showed coordinated activity while healthy volunteers rested and how closely activity in different regions varied together. In the 2018 experiment, 14 people received intranasal Semax and 10 received placebo. A medial-frontal part of the resting network occupied a larger scan-defined volume with Semax; this was a functional imaging result, not evidence that brain tissue grew. Neither report demonstrated improved memory, attention or everyday function on a corresponding task. Lebedeva and colleagues (2018), Panikratova and colleagues (2020).
Does N-terminal acetylation preserve every Semax effect?
A primary experiment found that acetylation changed copper coordination and removed a protective effect in a neuroblastoma-cell assay. Terminal chemistry can therefore change a measured response. That assay cannot rank the variants for clinical cognition or stroke recovery. Magrì and colleagues (2016).
Is there a measured human Semax half-life?
FDA's 2026 evaluation identified no human pharmacokinetic study for Semax free base or acetate. The rat distribution and peptide-breakdown experiments provide different information about the species and materials they measured. FDA (2026).
Comparisons and related reading
Selank illustrates a related Pro-Gly-Pro design built from a different parent sequence and studied mainly around anxiety. Oxytocin's profile connects physiological signaling with mixed behavioral trials. Epitalon's profile examines another case in which an exact synthetic peptide must be distinguished from a differently named preparation in the aging literature.
References
Full citations below identify the original clinical, imaging, animal and chemistry studies, together with current FDA records. Source annotations describe the particular evidence each record contributes.
In acute ischemic stroke, 30 patients given Semax were compared with 80 given conventional treatment. Movement problems and selected other neurological deficits improved faster with Semax added to intensive therapy.
Examines BDNF, motor performance and Barthel recovery among 110 patients grouped by rehabilitation timing and Semax exposure.
Reports scan-defined default-mode-network topography after an intranasal formulation in 14 recipients and 10 placebo participants.
Reports acute resting-state connectivity differences in 52 healthy participants; symptom and cognitive-task efficacy were not measured in the accessible abstract.
Identifies MEHFPGP and links rat hippocampal BDNF/TrkB measurements with a conditioned-avoidance response.
Reports immune- and vascular-associated transcriptional responses in the permanent-focal-ischemia rat setting.
Researchers examined rat brain 24 hours after temporarily blocking an artery and restoring blood flow. With Semax, inflammation-related RNA messages were reduced and messages associated with nerve-cell communication were increased.
Compares intact Semax and PGP responses in rat ischemic cortex, illustrating why the fragment does not carry every parent response.
Directly studies Ac-Semax chemistry; the acetylated form lost the parent's protective copper-toxicity response in SH-SY5Y cells.
Identifies Selank and Semax breakdown products through chromatographic separation of labeled peptides; the abstract supplies no human exposure curve.
Identifies substance-specific gaps in safety, aggregation, impurities and characterization for compounded peptide products.
Reviews form reporting, Russian registration, rat distribution and missing human PK, alongside clinical and nonclinical safety gaps.
Glossary
- ACTH
- Adrenocorticotropic hormone; Semax retains a short sequence related to its residues 4–7.
- BDNF
- Brain-derived neurotrophic factor, a signaling protein involved in neuronal function.
- TrkB
- A receptor through which BDNF can activate cellular signaling.
- Transcriptome
- The collection of RNA messages present in a sampled cell or tissue.
- Reperfusion
- Restoration of blood flow after its interruption.
- Barthel index
- A scale describing assistance needed for everyday activities.
- Default-mode network
- Brain regions with coordinated activity measured during rest.