N-Acetyl Semax Amidate

A doubly protected analogue of the Russian nootropic heptapeptide Semax, capped at both ends to slow enzymatic breakdown while retaining the neurotrophic signalling that defines the Semax family.

What it is

N-Acetyl Semax Amidate is a modified version of Semax, itself a synthetic heptapeptide based on the 4-10 fragment of adrenocorticotropic hormone (ACTH). The parent sequence is Met-Glu-His-Phe-Pro-Gly-Pro. In this variant the N-terminus carries an acetyl group and the C-terminus is amidated, giving the full structure Ac-Met-Glu-His-Phe-Pro-Gly-Pro-NH₂. It belongs to the same family of neuro-active research peptides developed in Russia as Selank and standard Semax.

The two terminal modifications are the whole point of the molecule. N-terminal acetylation blocks aminopeptidases that would otherwise trim residues from the free amino end, while C-terminal amidation blocks carboxypeptidases acting on the free carboxyl end. Capping both termini is intended to give the peptide greater resistance to proteolysis than unmodified Semax, which is a recurring theme in how vendors and secondary sources describe the compound. Published pharmacokinetic parameters specific to this analogue (plasma half-life, bioavailability, clearance) are not available, so most quantitative data below is drawn from the parent Semax literature and should be read as characterising the family rather than this exact molecule.

How it works

Semax and its analogues are studied as non-hormonal ACTH fragments: the ACTH-style corticotropic activity of the parent hormone is largely absent, and interest instead centres on neurotrophic signalling. In rat basal forebrain, radiolabelled Semax binds specific, calcium-dependent sites with a dissociation constant (K_D) of about 2.4 nM, indicating a discrete high-affinity interaction rather than diffuse membrane binding. Downstream, the peptide raises levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), the two neurotrophins most associated with synaptic plasticity, neuronal survival and cholinergic tone.

Mechanistically the neurotrophic effect is thought to run through the canonical BDNF/TrkB and NGF/TrkA cascades, which engage the MAPK/ERK, PI3K/Akt and PLC-gamma pathways that support long-term potentiation and neurogenesis. Semax also modulates the brain-derived neurotrophic system rapidly at the transcriptional level, with distinct time courses in the hippocampus versus the frontal cortex. Because N-Acetyl Semax Amidate shares the core heptapeptide, the same receptor-level and neurotrophic mechanisms are the working hypothesis for it, with the terminal caps expected mainly to prolong exposure rather than change the target.

What the research shows

The most concrete numbers come from rodent work on the parent peptide. Dolotov and colleagues (2006) characterised specific Semax binding in rat basal forebrain and showed that intranasal Semax raised BDNF protein there within hours. Gene-expression time-course work mapped rapid, region-specific activation of the Bdnf and Ngf genes. Human data is confined to Russian clinical studies, where Semax is an approved stroke therapy; one rehabilitation study measured a sustained rise in plasma BDNF in treated patients. The figures below are for Semax unless noted, and are reported as characterising the family. Supplied strictly for laboratory research use only, not for human or veterinary use.

Side Effects

There is no dedicated human safety trial for N-Acetyl Semax Amidate itself, so nothing about its tolerability can be stated from studies of the modified analog. What follows is inferred from the parent peptide, Semax (an ACTH(4-10) analog), which has been used in Russian neurological practice and studied mostly in animals and small clinical settings. Because the acetylated, amidated form is engineered to resist enzymatic breakdown and is reported to be more potent, its true effect and side-effect profile in humans is unknown and should not be assumed to match Semax.

In short, N-Acetyl Semax Amidate has no human side-effect profile of its own. Every point above is extrapolated from the parent peptide Semax, and the added stability and reported potency of the amidate mean its safety in humans is genuinely uncharacterized and cannot be assumed to be identical.

At a glance

Molecular formula C₃₉H₅₄N₁₀O₁₀S, sequence Ac-Met-Glu-His-Phe-Pro-Gly-Pro-NH₂, as listed under PubChem CID 172638603.

Dosing

No dedicated dosing study exists for N-Acetyl Semax amidate, so the figures below are drawn entirely from research on the parent peptide, Semax, and are shown for context rather than as a regimen for the amidate. The amidate is reported to be more stable, longer-acting, and more potent per microgram, so parent-Semax amounts cannot be assumed to translate one-to-one. All figures are historical study doses reported in the literature, not instructions, and are provided for laboratory research use only.

No established dose has been defined for N-Acetyl Semax amidate specifically, and because it is reportedly more potent and longer-acting than the parent peptide, the Semax figures above should not be read across to it directly. These entries are inferred study doses for a related compound, presented for educational purposes under a laboratory research-use-only framing.

Preparing it

N-Acetyl Semax Amidate is supplied as a lyophilised powder and is reconstituted with bacteriostatic or sterile water before use in the lab. Add the diluent slowly against the vial wall, let it dissolve without shaking, and store the reconstituted solution cold. See the reconstitution guide for step-by-step handling and the concentration guide for working out how much diluent gives the concentration you want.

Compared with standard Semax

Ordinary Semax carries a free N-terminus and, in some preparations, a C-terminal Pro-Gly-Pro tail intended to slow degradation. N-Acetyl Semax Amidate instead protects both ends chemically: acetylation at the amino terminus and amidation at the carboxyl terminus. The shared Met-Glu-His-Phe-Pro-Gly-Pro core means the neurotrophic pharmacology is expected to be the same in kind, with the practical difference framed as slower proteolysis and longer exposure rather than a new mechanism. Because no published study directly compares the two side by side in the same model, any potency ranking between them remains an open question in the literature.

Where to go next

Last updated on July 3, 2026