Semax Spray 50 mg

One-Peptides SEMAX 50 mg — ACTH(4-10) analogue nasal spray for laboratory research

This product is a reagent intended exclusively for scientific research (Research Use Only, RUO) conducted under laboratory conditions. It is not a medicinal product, a dietary supplement, a cosmetic or a medical device. It is not intended for consumption or for administration to humans or animals outside a strictly controlled, legally compliant research protocol. In the European Union, Semax holds no authorisation permitting its use for diagnostic or therapeutic purposes. The registration of Semax as an intranasal medicine in the Russian Federation is a separate regulatory framework that does not apply in the EU. Responsibility for the legally compliant storage, handling and use of the reagent rests with the research facility.

Semax originates from the Russian school of regulatory peptidology — the same scientific tradition that, since the 1980s, developed the idea of the rational modification of short fragments of endogenous proteins. The starting point here was the ACTH(4-10) fragment of adrenocorticotropic hormone: a team from the Institute of Molecular Genetics of the Russian Academy of Sciences took this segment of the sequence and redesigned it so as to preserve neurotropic activity while eliminating residual hormonal activity and extending the stability of the molecule in a biological environment. This is how the heptapeptide Semax came about — one of the best-documented neurotropic peptides in the Russian experimental literature, studied in a nootropic and neuroprotective context as well as in the context of neurotrophin modulation.

One-Peptides offers Semax as a pre-dissolved solution in a nasal spray, in a higher-content variant — 50 mg — as a research material with purity confirmed by HPLC. The choice of this format is not accidental. Semax is a peptide with a central action, and in the Russian literature and clinical practice it was studied precisely in the form of drops and a spray for intranasal administration — a route that has long interested neuroscience as a means of transporting neuropeptides along the nose-to-brain axis. The 50 mg variant addresses the needs of teams running longer series of experiments: a larger pool of material in a single package allows more dilutions and replicates to be planned without changing the reagent format. Below we present an honest picture of what is known about Semax from the literature, clearly separating data from research from the status of the reagent, and noting that a substantial part of the available work comes from the Russian literature with limited independent replication.

Semax is a synthetic heptapeptide built from seven amino acid residues with the sequence Met-Glu-His-Phe-Pro-Gly-Pro (MEHFPGP) and a molecular mass of approximately 813 Da. It is an analogue of the ACTH(4-10) fragment of adrenocorticotropic hormone, extended at the C-terminus by a Pro-Gly-Pro motif protecting against enzymatic degradation. It was developed at the Institute of Molecular Genetics of the Russian Academy of Sciences; in the literature it is analysed in a nootropic and neuroprotective context as well as in the context of the modulation of BDNF, TrkB and other neurotrophins. The 50 mg variant is the same molecule and the same quality as the 10 mg variant — the only difference is the larger peptide content intended for longer research series.

What Semax is — sequence and class

Semax belongs to the group of synthetic regulatory peptides designed as stable analogues of natural endogenous molecules. Its prototype is the ACTH(4-10) fragment — a segment of adrenocorticotropic hormone whose four N-terminal residues (Met-Glu-His-Phe) correspond to the ACTH(4-7) sequence and constitute the core with which neurotropic activity was associated in the literature. The problem with the natural fragment from a research perspective was its rapid proteolytic degradation, which is why the Russian team extended the sequence with a C-terminal Pro-Gly-Pro motif. The result is a heptapeptide with the sequence Met-Glu-His-Phe-Pro-Gly-Pro, considerably more resistant to the action of aminopeptidases and carboxypeptidases in serum and in nervous tissue.

The same design solution recurs in the related Selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro) — the proline residues adjacent to glycine form a structural anchor that hampers cleavage by proteolytic enzymes. This recurring Pro-Gly-Pro motif has become the hallmark of the Russian school of regulatory peptidology. Although Semax and Selank derive from different prototypes — the first from a fragment of ACTH, the second from tuftsin — they share the same design philosophy: take a short fragment of an endogenous protein, preserve its active core and add anti-degradation protection that extends the half-life from minutes to a few hours.

Chemical characterisation

The Met-Glu-His-Phe-Pro-Gly-Pro sequence is rich in proline residues at the C-terminus, which gives the peptide a more rigid conformation and reduces the number of sites susceptible to enzymatic cleavage. The N-terminal Met-Glu-His-Phe fragment corresponds to the ACTH(4-7) sequence and constitutes the core with which the biological activity of the molecule was associated in the literature. Its small mass, around 813 Da, places Semax in the group of small peptides — a feature of significance from the perspective of research on transport across biological barriers, including the nose-to-brain axis.

Mechanism of action in research

The mechanism of action of Semax has been described in the literature as pleiotropic — the peptide has been analysed in the context of effects on several signalling systems in parallel, without a single, isolated target receptor. The picture below derives from preclinical work, in large part from the Russian literature, and should be treated as a body of research hypotheses rather than confirmed effects in humans.

1. Modulation of BDNF and TrkB. The best-documented mechanistic direction. In animal models, the effect of Semax on the expression of brain-derived neurotrophic factor (BDNF) and its receptor TrkB in brain structures was analysed. Studies suggest that a single administration of the peptide to rats was associated with changes in the levels of BDNF and TrkB mRNA and protein in the hippocampus and cortex, which amplifies the neurotrophic signal (Dolotov et al., 2006). This cascade is analysed as one of the fundamental elements of the molecule’s neurotropic profile.
2. Neuroprotective action and gene regulation. In models of cerebral ischaemia, the action of Semax described as neuroprotective was studied. Analyses of gene expression pointed to the modulation of transcriptional profiles associated with the response to ischaemia, including inflammatory processes and the protection of neurons (Medvedeva et al., 2014). In this work the picture of neuroprotection was associated with a simultaneous effect on multiple pathways rather than with a single mechanism.
3. Effect on the neurotrophin system and neurotransmission. Beyond BDNF, the literature analysed the effect of Semax on other neurotrophins and on central neurotransmission, including the dopaminergic system. Some of the work associated these effects with the activating-nootropic profile observed in the models (Levitskaya et al., 2004). Here too the picture derives from preclinical research and requires cautious interpretation and further, independent verification.

Nasal spray format — research context

Intranasal administration has for years been analysed as a route that may facilitate the transport of selected molecules to the central nervous system, bypassing some of the barriers limiting systemic distribution — including the blood–brain barrier, a significant constraint for many neuropeptides. This mechanism, described as the nose-to-brain axis, is associated with the anatomical proximity of the olfactory epithelium and CNS structures and with transport along the pathways of the olfactory and trigeminal nerves.

In the case of Semax, the nasal spray format has an exceptionally strong grounding in the literature. Russian scientists studied Semax precisely in the form of drops and a spray for intranasal administration, and in the Russian Federation the intranasal route is the primary means of administering this molecule in clinical practice. This constitutes a genuine research precedent for this form, distinguishing Semax from peptides for which the rationale for a spray rests solely on the general logic of nose-to-brain transport.

Two things must, however, be clearly separated. The Russian research and the registration of intranasal Semax are one matter, and the status of the RUO reagent offered by One-Peptides is another — this is not a medicinal form and has no application in administration to humans. It should also be honestly noted that a substantial part of the available data comes from the Russian literature, and independent replication by Western research groups remains limited. Claims about the action profile of the peptide via this route of administration should therefore be treated as deriving from a particular body of research rather than as universally confirmed facts.

Semax RUO vs the Russian intranasal medicine

The most common source of misunderstanding around Semax is the equation of the research reagent with the medicine registered in Russia. These are two separate regulatory frameworks, even though the international name and the sequence are identical.

In the Russian Federation, Semax is clinically registered as a medicinal product in the form of drops and a nasal spray, with neurological indications including, among others, acute ischaemic stroke and selected cognitive disorders. This is a national registration — a separate, geographically limited regulatory framework that does not apply outside Russia.

In the European Union the situation is fundamentally different. Semax holds no marketing authorisation here as a medicinal product — neither from the EMA nor from any national registration authority. The reagent offered by One-Peptides is a Research Use Only product, that is, a chemical laboratory reagent, and not a medicinal form of Semax. Although the molecule is the same, the regulatory frameworks and intended uses are disjoint: the Russian intranasal medicine is intended for specific clinical indications, whereas the RUO reagent in the EU serves solely for research work in the laboratory.

The 50 mg variant — content and research work

The 50 mg variant differs from the 10 mg variant in one thing: the peptide content in the spray. The pre-dissolved nasal solution format, the sequence, the class of molecule, the mechanism analysed in the literature and the quality standard remain identical.

The higher content translates into a larger pool of research material in a single package. For teams planning longer series of experiments — dilution series, replication of conditions, comparisons between models or methodological studies of the route of administration itself — this means fewer packages to manage and a more consistent reference material originating from a single batch. From the perspective of reproducibility of results, working with material from a single series reduces batch-to-batch variability, which can be a significant factor in laboratory work. The choice between the 10 mg and 50 mg variants is therefore a matter of the scale of the planned project rather than a difference in the reagent itself.

Applications in scientific research

Semax in a nasal spray finds application in several areas of laboratory work, always within controlled research protocols conducted on in vitro and animal models.

1. In the area of neurotrophin pharmacology, the peptide is used as a reference material in research on the expression of BDNF, the TrkB receptor and other neurotrophic factors in brain structures. This work concerns changes at the mRNA and protein level and associated transcriptional profiles in rodent models and in cell cultures.
2. The second direction is neuroprotection models. Semax is analysed in cerebral ischaemia paradigms, in which its effect on neuronal survival, the modulation of the inflammatory response and the expression of genes associated with the response to ischaemia is studied. Work of this kind concerns exclusively animal and cellular experimental models and does not translate directly into effects in humans.
3. The third area is research on attention, memory and behaviour. Semax has been used in classical cognitive paradigms in rodents — modelling learning, the consolidation of the memory trace and responses to stimuli. Comparative work with the related Selank additionally provides a tool for studying mechanistic selectivity within peptides bearing the Pro-Gly-Pro motif. The nasal spray format also makes it possible to conduct methodological studies of the intranasal route of administration itself — of the stability of the peptide in solution, of kinetics, and of the comparison of different routes of administration in models.

One Peptides quality specification

One-Peptides supplies Semax as a research material of analytically confirmed quality, with full documentation accompanying every batch.

• HPLC purity ≥98% — each batch is analysed by high-performance liquid chromatography, which makes it possible to confirm the high degree of purity of the peptide. The peak area of the main peak constitutes at least 98% of the sum of the areas in the chromatogram.
• Identity confirmation by MS — mass spectrometry serves to verify the molecular mass and the identity of the sequence, which is a binding criterion for identification of the peptide.
• Certificate of analysis (COA) for each batch — a certificate is enclosed with each batch documenting the sequence, the theoretical and measured mass, the HPLC result and the batch number.
• Cold chain 2–8°C — the material is stored and transported under refrigerated conditions, which helps preserve its integrity.
• Batch traceability — the batch number makes it possible to link a specific package with the analytical documentation and the full history of its origin.

This range of quality control allows research teams to work with material of known and documented characterisation, which is a condition of the reproducibility of results in laboratory work. In the 50 mg variant the control standard is identical to that in the 10 mg variant — they differ solely in peptide content.

Safety and limitations

In animal models Semax was generally described as a well-tolerated peptide, without clear signals of toxicity within the range of the experimental conditions analysed. Some of the Russian work, including clinical studies conducted in centres there, pointed to a favourable tolerability profile also with intranasal administration. Far-reaching conclusions should not, however, be drawn from this — these observations come from a particular body of research and have not been widely replicated by independent Western groups.

The most important limitation remains the scarcity of independent data. A substantial part of the literature concerning Semax comes from the Russian literature, and a rigorous, independently replicated base of research — especially large, independent randomised controlled trials (RCTs) outside Russian centres and long-term data under European conditions — is limited. The absence of documented warning signals in the available work is not equivalent to a confirmed, universal safety profile.

For this reason Semax remains a material of an exclusively research character, and any observations regarding its action should be related to the experimental context in which they were obtained. Work with the reagent should be carried out in accordance with the principles of good laboratory practice and the appropriate safety procedures, by qualified personnel.

Regulatory status and WADA

Semax is classified as a research reagent (Research Use Only) and is offered in that capacity. In the European Union the peptide holds no registration as a medicinal product, nor is it authorised as a dietary supplement or a medical device. It holds no marketing authorisation issued by the EMA or any national registration authority in the EU. This means that it is not subject to the authorisation procedures proper to medicines and may not be presented as an agent of established therapeutic action.

The registration of Semax as an intranasal medicine in the Russian Federation constitutes a separate, geographically limited regulatory framework that does not apply in the EU. The RUO reagent sold in the EU — including by One-Peptides — is not a medicinal form of Semax, regardless of the existence of the Russian registration.

With regard to anti-doping regulations, according to the available information Semax does not appear by name on the list of prohibited substances and methods of the World Anti-Doping Agency (WADA). The regulatory status of a substance may, however, change, and the interpretation of prohibited lists can be complex. For this reason verification of the current status — both anti-doping and legal in a given jurisdiction — remains the responsibility of the researcher and the institution conducting the research. One-Peptides does not provide legal or regulatory advice.

Frequently asked questions

What is Semax?
Semax is a synthetic heptapeptide with the sequence Met-Glu-His-Phe-Pro-Gly-Pro (MEHFPGP) and a mass of about 813 Da, developed at the Institute of Molecular Genetics of the Russian Academy of Sciences. It is an analogue of the ACTH(4-10) fragment of adrenocorticotropic hormone, extended at the C-terminus by a Pro-Gly-Pro motif protecting against enzymatic degradation. One-Peptides offers it as a reagent for laboratory research (RUO), not as a product for use in humans.

What does the research say about BDNF and neuroprotection?
In animal and cellular models, the effect of Semax on the expression of brain-derived neurotrophic factor (BDNF) and its receptor TrkB was analysed, and in models of cerebral ischaemia an action described as neuroprotective was studied, associated with the modulation of the expression of ischaemia-response genes. Two things must, however, be emphasised: these are observations from experimental models rather than a confirmed effect in humans, and a substantial part of the data comes from the Russian literature with limited independent replication. This remains a research area rather than an established clinical fact.

How does the 50 mg variant differ from the 10 mg variant?
The only difference is the peptide content in the spray. The pre-dissolved nasal solution format, the sequence, the class of molecule, the mechanism analysed in the literature and the quality standard (HPLC ≥98%, MS, COA per batch, cold chain) are identical. The 50 mg variant is a larger pool of material intended for longer research series — a dilution series, replicates and comparisons conducted on material from a single batch. The choice between the variants is a matter of the scale of the planned project.

What is the difference between the RUO reagent and the Russian intranasal medicine?
In the Russian Federation, Semax is registered as a medicine in the form of drops and a nasal spray with neurological indications — this is a national registration, a separate, geographically limited regulatory framework. In the European Union, Semax holds no registration as a medicinal product. The reagent offered by One-Peptides is a Research Use Only product, that is, a chemical laboratory reagent, and not a medicinal form. The molecule is the same, but the regulatory frameworks and intended uses are disjoint.

How should the material be stored to preserve stability?
Semax in the form of a pre-dissolved solution requires storage under refrigerated conditions, in the range of 2–8°C (cold chain), with limited exposure to light and to repeated temperature fluctuations. The Pro-Gly-Pro motif at the C-terminus increases the peptide’s resistance to degradation, which favours its stability in solution — Semax is more stable than most short regulatory peptides. Detailed stability recommendations are provided in the certificate of analysis (COA) enclosed with each batch. The material should be handled in accordance with the rules applicable to research reagents.

Bibliography

1. Dolotov OV et al. (2006). Semax, an analog of ACTH(4-10), regulates expression of BDNF and trkB in the rat brain
2. Medvedeva EV et al. (2014). The peptide semax affords neuroprotection — gene expression analysis
3. Levitskaya NG et al. (2004). Effects of Semax in a model — behavioral physiology
4. Ashmarin IP et al. (1997). Semax — synthetic analog of ACTH(4-10): pharmacological characteristics (DOI not verified — no link)

This material is a reagent intended exclusively for research purposes (Research Use Only). It is not a medicinal product, a dietary supplement or a medical device, and it may not be used in diagnostics or therapy in humans or animals. The information contained in the description is of a scientific and informational character, relates to data from the literature obtained under experimental conditions — in large part from the Russian literature with limited independent replication — and does not constitute medical, pharmaceutical or legal advice. The registration of Semax as an intranasal medicine in the Russian Federation is a separate regulatory framework that does not apply in the EU. All operations involving the reagent must be carried out by qualified personnel under laboratory conditions, in accordance with the applicable regulations. Full responsibility for the legally compliant use of the material rests with the purchaser.