N-Acetyl Semax spray

Chemical reagent intended exclusively for laboratory tests (Research Use Only). It is not a medicinal product, dietary supplement or food. It is not intended for use on humans or animals. Sales only to registered research units and laboratories.

Native Semax degrades in serum within minutes – the heptapeptide with the sequence Met-Glu-His-Phe-Pro-Gly-Pro (MEHFPGP) is an attractive neuropharmacological tool, but its half-life limits the observation window in many protocols. N-Acetyl Semax is the response of peptide chemistry to this limitation: the same core sequence as Semax, with a terminal modification in the form of N-terminal acetylation (Ac-Met-Glu-His-Phe-Pro-Gly-Pro).

Acetylation of the α-amino group blocks the site of attack by aminopeptidases that degrade the free N-end, which in research models translates into longer durability of the peptide in solution and tissue. This reagent is supplied in a spray preparation kit containing lyophilisate, water and an atomizer. The solution must be prepared from the lyophilisate before research work.

This format reflects the dominant route of administration in the literature for the Semax family – native Semax is registered in the Russian Federation as nasal drops and spray, and intranasal administration of regulatory peptides is standard in preclinical protocols examining nose-to-brain transport. The same compound in a classic vial is available as N-acetyl Semax 50mg — lyophilisate for reconstitution to the experimental parameters.

In terms of its pharmacological profile, N-Acetyl Semax inherits the mechanisms of Semax: strong induction of BDNF and NGF in the hippocampus and cortex, an ACTH(4-7) analogue profile devoid of corticotropic activity, modulation of dopaminergic and serotonergic transmission, inhibition of enkephalinases and neuroprotective activity in ischemia models. Within a category peptides for brain function it is located on the side of the nootropic-neuroprotective axis. Purity verified by HPLC ≥98%, identity confirmed by mass spectrometry, COA available for each batch.

N-Acetyl Semax is not registered as a medicine in the EU or USA. Native Semax is registered as a medicinal product only in the Russian Federation – the modified N-acetylated analogue does not have such registration in any jurisdiction. Communicating the product as an “over-the-counter nootropic”, “concentration spray” or “memory booster” is inconsistent with the Research Use Only framework.

Semax was born from a simple observation: the ACTH(4-10) fragment – a seven-amino-acid fragment of the adrenocorticotropic hormone – has an effect on memory and learning in animal models, but is devoid of hormonal activity (does not stimulate the secretion of corticosteroids). The problem was instability: the ACTH fragment was rapidly proteolytically degraded. The team at the Institute of Molecular Genetics in Moscow redesigned this molecule, shortening it to the ACTH(4-7) fragment — Met-Glu-His-Phe — and adding the C-terminal tripeptide Pro-Gly-Pro.

Semax (MEHFPGP) was created: a peptide that retains the neurotropic profile of the ACTH fragment, but is clearly more stable due to the presence of proline residues that hinder the action of peptidases. Pro-Gly-Pro serves as a chemical stabilizer here – peptide bonds involving proline are resistant to most endopeptidases. This is the same design logic used in the related Selank (also finished with Pro-Gly-Pro).

N-Acetyl Semax goes one step further: it adds N-terminal acetylation to the proline strategy, closing another gate for aminopeptidases attacking the free amino group of methionine.

N-Acetyl Semax is a synthetic heptapeptide – N-acetylated derivative of Semax, an analogue of the ACTH(4-7) fragment extended with Pro-Gly-Pro.

• Common name: N-Acetyl Semax, NA-Semax, acetylated Semax
• Sequence: Ac-Met-Glu-His-Phe-Pro-Gly-Pro (single letter: Ac-MEHFPGP)
• Modification compared to Semax: acetylation of the α-amino group of the N-terminus (methionine) – blockade of the attack site of aminopeptidases
• Chemical class: modified regulatory heptapeptide; a synthetic analogue of the ACTH(4-7) fragment with the Pro-Gly-Pro tripeptide attached
• Molar mass: ~855 g/mol (Semax core ~813 Da + acetyl group +42 Da; exact value – to be verified in the batch COA)
• CAS: for verification in the batch COA (native Semax: 80714-61-0; acetylated form requires confirmation on a certificate)
• pH / nature: the core contains a histidine residue (buffering in the physiological range) and glutamic acid; acetylation of the N-terminus reduces the positive charge
• Supplied form: spray preparation kit containing lyophilisate, water and an atomizer; reconstitution before research work; pharmaceutical grade ≥98% HPLC

Origin and modification logic: The pharmacophore core comes from a natural hormone – the Met-Glu-His-Phe fragment corresponds to positions 4–7 of the ACTH sequence. It is this section that is responsible for the neurotropic effect of melanocortins in the central nervous system, regardless of the hormonal axis. Attaching Pro-Gly-Pro to the C-terminus transformed the unstable hormone fragment into a more stable regulatory peptide with a nootropic and neuroprotective profile.

N-acetylation of the N-terminus is another standard step in the chemistry of regulatory peptides to extend proteolytic stability: capping the free amino group blocks aminopeptidases that degrade the peptide from the N-terminus, without changing the core responsible for binding to molecular targets.

SCIENTIFIC PERSPECTIVE

Some of the data quoted for this reagent comes from the literature on native Semax (MEHFPGP), not its N-acetylated analogue. The final modification changes the pharmacokinetics (stability, distribution profile) and potentially also the affinity for molecular targets. Extrapolating the Semax profile to N-Acetyl Semax is a working hypothesis, not a documented fact – it requires independent validation for the modified molecule. Moreover, most of the mechanistic work on the Semax family comes from Russian-speaking groups and was carried out in animal models and in vitro.

N-Acetyl Semax – as a derivative of Semax – probably works through several parallel neurobiological pathways. The following mechanisms have been documented for native Semax in preclinical models; their transfer to the acetylated analogue remains under investigation. Pharmacological profile described for the Semax family in research models:

1. Strong induction of BDNF and NGF (neurotrophic factors) — the best described and most characteristic mechanism. Semax in rat models increases the expression of BDNF (brain neurotrophic factor) and NGF (nerve growth factor) in the hippocampus and cortex, along with the activation of their TrkA and TrkB receptors (Dolotov et al. 2006). This is a probable basis for the influence on synaptic plasticity, neurogenesis and neuronal survival. The neurotrophic profile of Semax is clearly stronger than that of the related Selank – this is the difference that distinguishes the nootropic-neuroprotective axis from the anxiolytic axis
2. ACTH(4-7) analogue without corticotropic activity — Met-Glu-His-Phe core comes from melanocortin, but Semax does not stimulate the secretion of cortisol or corticosterone. The neurotropic activity of the ACTH fragment has been separated from its hormonal function – the peptide acts at the level of the central nervous system, not at the level of the hypothalamic-pituitary-adrenal axis. This is an important feature of profile security in research models
3. Modulation of dopaminergic and serotonergic transmission — Semax in animal models affects the dopamine system (including in the structures of the striatum and prefrontal cortex) and the serotonergic system, which is related to the observed pro-cognitive profile and the impact on motivation and mood in behavioral tests. Modulation of monoamines is a probable co-mechanism of nootropic action
4. Inhibition of enkephalinases — Semax inhibits the activity of enkephalin-degrading enzymes in serum and brain tissue (Kost et al. 2001), which increases the concentration of endogenous Met- and Leu-enkephalins in synapses. Prolonged activity of endogenous opioid peptides likely contributes to neuroprotective and mood-stabilizing effects
5. Neuroprotection in ischemia models — in models of cerebral ischemia (experimental stroke, hypoxia), Semax reduces the area of ​​damage and affects neuronal survival markers and the inflammatory response (Medvedeva et al. 2014). This is the basis for the most widely researched direction of applications of native Semax in Russian experimental neurology

The nasal spray format refers to the dominant route of administration in the literature over the Semax family. The molecular logic is well described in peptide neuropharmacology, and the format itself fits into a broader group peptides spray intended for intranasal administration. Most regulatory peptides do not cross the blood-brain barrier (BBB) ​​well when administered peripherally – they are too large and too polar. Intranasal administration offers an alternative delivery route to the central nervous system (CNS), partially bypassing the BBB. Two parallel nose-to-brain transport pathways have been described in research models:

• Olfactory pathway (olfactory) — a peptide applied to the olfactory epithelium in the upper part of the nasal cavity can be transported along the olfactory nerves directly to the olfactory bulb and further to the structures of the forebrain, bypassing the systemic circulation
• Trigeminal nerve pathway — the endings of the trigeminal nerve innervating the nasal mucosa constitute a second route of transport to the brain stem and further structures of the CNS

In research models, intranasal administration of regulatory peptides demonstrates nose-to-brain transport, achieving higher concentrations in brain structures at lower total doses than systemic administration. For the Semax family, the intranasal route is preferred in preclinical protocols for this very reason – the short half-life of the peptide in the blood makes direct transport to the CNS, bypassing the systemic circulation, particularly important.

The separation of these two molecules is the most important substantive caveat of this description. N-Acetyl Semax (Ac-MEHFPGP) and native Semax (MEHFPGP) share an identical pharmacophore core but differ in N-terminal modification, which has practical consequences:

• Proteolytic stability — N-terminal acetylation blocks aminopeptidases, so the acetylated analogue is designed to be more stable in solution and tissue than native Semax. This is the main intention of the modification
• Pharmacokinetics of nasal transport — changing the charge and lipophilicity of the N-terminus affects the kinetics of penetration through the olfactory epithelium. The nose-to-brain profile of native Semax does not translate 1:1 to the acetylated analogue
• Data portability — almost all documented literature (BDNF/NGF, neuroprotection, clinical precedent for intranasal administration) concerns native Semax. The acetylated analog profile is a working hypothesis derived from core similarity, not a set of independently confirmed observations

The starting form for this family is the unmodified peptide available as Semax 50mg (MEHFPGP core, nootropic-neuroprotective axis) – the durability and kinetics of the acetylated analogue are compared to it. An analogous caution applies to the related Selank: the precedent of intranasal administration of native Selank and native Semax (both registered in the Russian Federation as nasal formulations) is a strong argument for the logic of the intranasal route for the entire family, but is not evidence for N-acetylated forms.

The peptide sequence and mass confirmation by MS remain the only binding signals of identity – the label and trade name alone do not determine whether the package contains the native or acetylated form.

N-Acetyl Semax in a nasal spray format is used in research directions analogous to native Semax, with additional emphasis on characterizing the profile of the modified molecule:

• Neuroprotection models — experimental models of cerebral ischemia, hypoxia and neuronal damage; assessment of the effect of the acetylated analogue on the area of ​​damage, markers of neuronal survival and inflammatory response
• Research on neurotrophic factors — expression of BDNF and NGF and activation of Trk receptors in the hippocampus and cortex; comparison of the kinetics and induction strength of the acetylated analogue versus native Semax
• Cognitive models — memory and learning tests (Morris water maze, passive avoidance, radial arm maze), especially in conditions of cognitive impairment caused by stress, ischemia or neurotoxins
• Nose-to-brain transport studies — comparative pharmacokinetics of intranasal versus systemic administration; characterization of the effect of N-terminal acetylation on transport through the olfactory epithelium and achieved concentrations in brain structures
• Models of monoaminergic transmission — influence on the dopamine and serotonergic systems in the structures of the striatum, prefrontal cortex and hippocampus; research on the basis of the procognitive profile
• Models of stress and adaptation — assessment of the impact on resistance to chronic stress and markers of synaptic plasticity, in comparison with the Selank anxiolytic axis.

N-Acetyl Semax Spray is an N-acetylated derivative of Semax (Ac-MEHFPGP), an analogue of the ACTH(4-7) fragment extended with Pro-Gly-Pro – supplied as a kit containing lyophilisate, water and an atomizer. The solution must be prepared before research work according to the batch documentation. N-terminal acetylation blocks aminopeptidases, extending the stability of the peptide in solution.

The pharmacological profile inherited from Semax includes strong BDNF and NGF induction, a neurotrophic profile of the ACTH fragment without corticotropic activity, modulation of dopaminergic and serotonergic transmission, inhibition of enkephalinases, and neuroprotection in ischemia models – all documented for native Semax in rodent and in vitro models, with the need for separate validation for the acetylated analogue.

The spray format refers to the nasal route of the Semax family dominating in the literature and the nose-to-brain transport mechanism. Regulatory status – Research Use Only.

1. Dolotov OV, Karpenko EA, Inozemtseva LS, Seredenina TS, Levitskaya NG, Rozyczka J, et al. (2006). Semax, an analogue of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. PubMed
2. Medvedeva EV, Dmitrieva VG, Povarova OV, Limborska SA, Skvortsova VI, Myasoedov NF, Dergunova LV (2014). The peptide semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia: genome-wide transcriptional analysis. PubMed
3. Shadrina M, Kolomin T, Agapova T, Agniullin Y, Shram S, Slominsky P, et al. (2010). Comparison of the temporary dynamics of NGF and BDNF gene expression in rat hippocampus, frontal cortex, and retina under Semax action. PubMed
4. Ashmarin IP, Nezavibatko VN, Myasoedov NF, Kamensky AA, Grivennikov IA, Ponomareva-Stepnaya MA, et al. (1997). A nootropic adrenocorticotropin analog 4-10-Semax (15 years of experience in its design and study). PubMed
5. Kaplan AYa, Koshelev VB, Nezavibatko VN, Ashmarin IP (1992). Increased resistance to hypoxia effected by the neuropeptide preparation Semax. PubMed
6. Kost NV, Sokolov OY, Gabaeva MV, Grivennikov IA, Andreeva LA, Myasoedov NF, Zozulya AA (2001). Semax and selank inhibit the enkephalin-degrading enzymes from human serum. PubMed