N-Acetyl Semax Amidate

NA-Semax, N-acetyl Semax amide, Ac-Semax-NH2; parent compound Semax (Met-Glu-His-Phe-Pro-Gly-Pro)

Cognitive & neuro
Awaiting medical reviewEN ES DE FR PT ZH+ Follow for updates

1What it is

Semax is a Russian-developed neuropeptide, created at the Institute of Molecular Genetics in Moscow (Myasoedov, Ashmarin and colleagues) from the 4–7 fragment of the stress hormone ACTH, with a Pro-Gly-Pro tail added so it survives longer in the body. It has been approved in Russia since the 1990s as nasal drops for stroke, cognitive disorders and optic-nerve conditions, and is covered in its own profile (#36).

"N-Acetyl Semax Amidate" is a chemically modified version in which the free amino group at one end is capped with an acetyl group and the free acid at the other end is converted to an amide. These two changes are standard peptide-chemistry tricks to make a peptide less vulnerable to enzymes that chew from either end. The derivative appears to have originated in the research-chemical community rather than in a laboratory programme: we are not aware of any peer-reviewed study — pharmacological, pharmacokinetic or clinical — that tests NA-Semax amidate specifically. Everything written about its effects is either extrapolated from Semax or anecdotal. This profile therefore borrows the parent's science and is explicit about what has not been shown.


2How it's thought to work

Assuming the caps do not change receptor behaviour (unproven), the mechanisms proposed for Semax apply:

Neurotrophins. Intranasal Semax increases BDNF and its receptor TrkB in rat hippocampus within hours (Dolotov 2006) and NGF/BDNF in the basal forebrain (Shadrina 2001).
Gene expression after ischaemia. In rat stroke models Semax shifts expression of immune, vascular and neurotransmitter-related genes toward recovery (Medvedeva 2013/2014, Stavchansky).
Enkephalinase inhibition. Semax and Selank inhibit enzymes that degrade enkephalins in human serum (Kost 2001), a plausible contributor to mood and attention effects.
Melanocortin lineage without classic receptor action. Semax is derived from ACTH but does not stimulate cortisol release and does not act as a conventional melanocortin receptor ; the exact receptor is still debated.
What the caps add. In theory: slower breakdown, longer exposure, perhaps better nasal-to-brain delivery. In practice: no data. End-capping can also reduce receptor binding for some peptides, so "more stable" does not automatically mean "more active".
Proposed: a stabilised analogue of Semax, itself a fragment of ACTH(4-10) without hormonal activity, reported to raise BDNF and NGF. The amidated form is intended to resist breakdown; the human evidence remains thin outside Russian clinical use.Schematic — not to scale

3What the research shows

Any effect of NA-Semax amidate specifically

No published human or animal study. This is the central fact of the profile.
Graded B (Russian clinical literature)

Parent compound, ischaemic stroke

Semax 1% nasal drops in acute ischaemic stroke were associated with better neurological recovery in Russian clinical studies from the 1990s–2000s (Gusev and colleagues, Zh Nevrol Psikhiatr Im S S Korsakova). Many were open or historically controlled; none meets modern multicentre standards.

Parent compound, attention and memory in healthy adults

A small controlled study reported improved attention and memory performance after intranasal Semax in healthy volunteers (Kaplan 1996). Small, single-site. [5]

Parent compound, neurotrophin and gene-expression effects

Robust and repeatedly shown in rats (Dolotov 2006; Medvedeva 2013). This is the strongest part of the Semax literature and the part most often cited to justify the derivative. [1][3]

Community-reported effects

Members describe sharper focus, calmer mood and better verbal fluency for a few hours after a nasal dose, sometimes with a comparison that NA-Semax "feels stronger or longer" than Semax. No controlled comparison exists.

4Reported side effects and interactions

Literature-reported

none for the derivative. Semax itself is reported as well tolerated in Russian studies, with nasal irritation the main complaint.

Community-reported

nasal stinging or dryness, headache, over-stimulation or anxiety at higher doses, sleep disruption if used late, hair-loss anecdotes that recur online without any literature support, and occasional "flatness" or irritability on stopping.

Theoretical. acetylation and amidation change how a peptide is metabolised; unknown breakdown products are a real, if unquantified, consideration. ACTH-derived peptides in theory touch the melanocortin system (pigmentation, appetite, stress axis); Semax does not appear to raise cortisol, but the derivative has not been checked.

Interactions. none established. Additive stimulation with caffeine or stimulants is commonly reported.

Markers researchers commonly monitor

No compound-specific markers exist; these follow from the parent's biology:

MarkerWhy it's watched
Morning cortisolSemax is an ACTH fragment; it is reported not to raise cortisol, but the derivative has never been checked, and a baseline/follow-up is cheap.
Blood pressure and resting heart ratecommunity reports of over-stimulation; melanocortin-related peptides can affect autonomic tone.
Sleep loginsomnia with late dosing is the commonest complaint.
A repeatable attention/memory testthe only way to separate a real cognitive effect from expectation.
CBC and CMPgeneral baseline for an unstudied derivative.

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5Reconstitution and handling

Usually supplied as powder in vials of a few milligrams, or pre-mixed as a nasal spray. For nasal use the powder is with sterile or and transferred to a metered spray bottle; the dose per spray depends entirely on the concentration and the bottle's spray volume (commonly ~0.1 ml), so both numbers are needed. Peptides with free histidine and methionine (Semax has both) are sensitive to oxidation: refrigerate, keep away from light, and discard solutions that discolour.

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6Commonly studied alongside

Semax (#36, the parent) and Selank (#37) are the natural comparators; N-Acetyl Selank Amidate (#93) is the matching derivative and the two are often used as a "focus and calm" pair in community practice. Also discussed with Noopept (#91), Cerebrolysin, P21 and Dihexa, without combined data.

Informational cross-links. Not stack recommendations.


7Regulatory status by region

RegionStatus (checked —)
United StatesNot FDA-approved; not an approved compounding substance. The derivative is not the molecule covered by any regulatory file †
European UnionNot authorised
United KingdomNot licensed
AustraliaNot approved
South AfricaNot registered
RussiaSemax (not the derivative) is an approved medicine; NA-Semax amidate has no approval
Sport (WADA)Not specifically listed; as a non-approved pharmacological substance it would fall under S0 †

8Open questions

  • Does NA-Semax amidate bind and act like Semax at all? No receptor or cell data exist.
  • Pharmacokinetics: is it actually longer-lasting, and does more reach the brain intranasally?
  • Any human safety data — currently none.
  • What the metabolites are, and whether acetylated fragments have their own activity.

9References

  1. 1Dolotov OV et al. (2006). Semax, an analog of ACTH(4–10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. Brain Res. PubMed · DOI
  2. 2Shadrina MI et al. (2001). Rapid induction of neurotrophin mRNAs in rat glial cell cultures by Semax, an adrenocorticotropic hormone analog. Neurosci Lett. PubMed · DOI
  3. 3Medvedeva EV et al. (2013). Semax, an analog of ACTH(4–7), regulates expression of immune response genes during ischemic brain injury in rats. Mol Genet Genomics. PubMed
  4. 4Kost NV et al. (2001). Semax and Selank inhibit the enkephalin-degrading enzymes from human serum. Bioorg Khim. PubMed · DOI
  5. 5Kaplan AYa et al. (1996). Synthetic ACTH analogue Semax displays nootropic-like activity in humans. Neurosci Res Commun. DOI
  6. 6Gusev EI et al. (various, 1997–2005). Clinical studies of Semax in acute ischaemic stroke. Zh Nevrol Psikhiatr Im S S Korsakova [identify specific papers before publishing]. PubMed

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.


10Community

Threads and protocols are visible to members. Joining is free.

Self-reported side effects Phase 2

Not enough data yet. 0 of the 50 members needed have logged this compound for 4+ weeks. We don't show anything below 50, so no one can be identified.

11Page history

26 Oct 2026Profile published — awaiting medical review

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