# N-Acetyl Semax Amidate — Research Peptide Profile

> N-Acetyl Semax Amidate (Ac-MEHFPGP-NH2) is catalogued in PubChem but untested in any published study. Structure, Semax evidence, and safety status.

Source: https://peptpedia.org/peptide/na-semax-amidate | Published: 2026-09-18 | Last updated: 2026-09-18

N-Acetyl Semax Amidate is Semax with both reactive ends capped: an acetyl group at the N-terminus and an amide at the C-terminus (Ac-Met-Glu-His-Phe-Pro-Gly-Pro-NH2). The structure is documented in PubChem (CID 172638603, CAS 2920938-90-3), yet no peer-reviewed study has tested the analog in any model. The closest evidence base is the Russian clinical and preclinical literature on unmodified Semax, which does not automatically transfer to the end-capped form.

## Overview

N-Acetyl [Semax](/peptide/semax) Amidate (often shortened to NA-Semax-Amidate) is the simplest of the vendor-market Semax derivatives: the unaltered Semax heptapeptide sequence (Met-Glu-His-Phe-Pro-Gly-Pro) with an acetyl cap on the N-terminus and an amide cap on the C-terminus. Unlike most grey-market analogs, its exact structure is authoritatively documented in PubChem (CID 172638603; C39H54N10O10S, 855.0 g/mol; CAS 2920938-90-3), which removes identity ambiguity but not the evidence gap: PubMed contains no pharmacology, toxicology, or clinical literature for the analog under any of its names. The modifications are aimed at the known weakness of Semax, its minutes-long plasma half-life, by blocking the aminopeptidase and carboxypeptidase attack that the native ends invite. The parent compound is a registered drug in Russia with human stroke studies, placebo-controlled fMRI work in healthy volunteers, and a deep rodent literature on BDNF, neuroprotection, and gene expression. None of that literature tested the end-capped form, so this profile documents what the parent molecule established and marks clearly where direct evidence stops.

## Molecular Profile

- **Category:** cognitive-enhancement
- **Molecular formula:** C39H54N10O10S
- **Molecular weight:** 855.0 g/mol
- **CAS number:** 2920938-90-3
- **Amino acid sequence:** Ac-Met-Glu-His-Phe-Pro-Gly-Pro-NH2
- **Also known as:** NA-Semax-Amidate, N-Acetyl Semax, Acetyl Semax Amidate, NA Semax
- **Half-life:** Not measured for the amidate; unmodified Semax clears plasma in 2-3 minutes
- **Solubility:** Soluble in water (inferred from the Semax core)
- **Storage:** No validated stability data; lyophilized peptides of this class are typically stored at -20°C.

## Mechanism of Action

No mechanism has been measured for the amidate analog. For unmodified Semax, the documented mechanisms are: upregulation of BDNF and NGF expression in hippocampus, cortex, and basal forebrain; modulation of striatal serotonergic transmission with potentiation of evoked dopamine release; inhibition of enkephalin-degrading enzymes; and broad regulation of immune-response and vascular genes during ischemic brain injury. Semax carries no steroidogenic activity despite its ACTH(4-10) origin. The end caps of the amidate are intended to preserve these actions while extending molecular survival; in principle they could also alter potency or receptor selectivity, and no binding, gene-expression, or behavioral assay has resolved that question.

## Key Research Findings

- Unlike most grey-market analogs, N-Acetyl Semax Amidate has an authoritative identity: PubChem CID 172638603, C39H54N10O10S, 855.0 g/mol, CAS 2920938-90-3.
- The analog has zero published studies; every biological claim is inherited from unmodified Semax.
- Its design targets Semax's documented weakness, a 2-3 minute plasma half-life, but no stability or potency measurement of the analog exists.
- Semax's bioactive C-terminal PGP fragment is exactly the region the amide cap modifies, an untested interaction flagged by the parent literature itself.

## N-Acetyl Semax Amidate Pharmacokinetics: A Stability Hypothesis, Not a Measurement

The entire rationale for this analog is pharmacokinetic, yet no pharmacokinetic parameter has ever been published for it. What follows is the documented behavior of unmodified Semax and the class-level effect of end capping.

### The Problem the Analog Was Built to Solve

- Unmodified Semax has a plasma half-life of about 2-3 minutes due to rapid cleavage by enkephalinase and carboxypeptidase; its Pro-Gly-Pro tail provides only partial protection.
- Despite fast plasma clearance, Semax triggers CNS gene-expression programs that persist 24-48 hours, so biological effect duration decouples from plasma presence (PMID: 14556513).
- In a rat global-ischemia model, both Semax and its C-terminal tripeptide fragment PGP regulated neurotrophin and receptor expression, indicating the tail fragment itself is bioactive; capping the C-terminus as an amide changes that fragment chemistry in ways that have not been assayed (PMID: 22295573).

### What the End Caps Should Change, and What Is Unknown

- N-terminal acetylation removes the substrate recognized by aminopeptidases; C-terminal amidation removes the carboxylate recognized by carboxypeptidases. For most peptides this extends serum survival, but no serum stability assay of the Semax amidate has been published.
- Intranasal Semax produces measurable human CNS effects within 5-20 minutes in placebo-controlled fMRI work (PMID: 30225715); vendor protocols for the amidate use the same route or injection, with no comparative exposure data for the analog.
- The PubChem registration (CID 172638603) fixes the structure and formula, which at least makes the analog chemically unambiguous for any future formal study.

## Safety & Tolerability

N-Acetyl Semax Amidate has no direct safety data: no published study has administered it to any species. The adjacent evidence is the Semax human record, which includes a 110-patient stroke series and a placebo-controlled volunteer study without reported drug-related safety signals, but the end-capped analog is a distinct chemical entity whose behavior is unmeasured.

**Human data status:** No human data exists for the amidate analog. Unmodified Semax has published human interventional studies in stroke patients and healthy volunteers; the analog has none.

**Regulatory status:** Not approved anywhere. Semax is a registered drug in Russia and Ukraine; the amidate is an unregulated research chemical.

- No peer-reviewed study of N-Acetyl Semax Amidate exists; the compound is registered in PubChem but has no pharmacology, toxicology, or clinical literature. (evidence tier: theoretical)
- In 110 ischemic stroke patients, unmodified Semax (10-day courses of 6000 mcg/day) raised plasma BDNF without a reported drug-related safety signal in that publication; this documents Semax, not the amidate. (evidence tier: human-interventional; [PMID 29798983](https://pubmed.ncbi.nlm.nih.gov/29798983/))
- In a placebo-controlled fMRI study, single intranasal 1% Semax doses in 24 healthy adults altered default mode network measures without reported adverse effects, documenting acute parent-compound tolerability only. (evidence tier: human-interventional; [PMID 30225715](https://pubmed.ncbi.nlm.nih.gov/30225715/))
- Semax's C-terminal PGP fragment is itself bioactive in ischemia models; the amide cap modifies exactly this region, and the safety or activity consequence of that change has never been assayed. (evidence tier: animal; [PMID 22295573](https://pubmed.ncbi.nlm.nih.gov/22295573/))

## Dosing Information (Research Context)

No published dosing data exists for N-Acetyl Semax Amidate in any species. Unmodified Semax has been dosed intranasally at 200-600 mcg daily in Russian cognitive protocols and at 6000 mcg/day in 10-day stroke courses. Nothing published establishes how the end caps change potency, distribution, or duration, so any analog-specific dosing figure is anecdotal.

## Researched Effects

- **Cognitive Enhancement (Extrapolated From Semax)** (evidence: preliminary): Claims of improved focus, memory, and mental-fatigue resistance for the amidate rest on the parent literature: Semax improved attention and memory measures in Russian clinical use, and a placebo-controlled fMRI study showed single intranasal doses changed default mode network measures in healthy adults within 20 minutes (PMID: 30225715). No study has administered the amidate analog to humans or animals, so all cognitive claims are extrapolations.
- **Neuroprotection in Ischemia (Parent Compound)** (evidence: preliminary): Semax has a substantial preclinical ischemia record: regulation of immune-response genes during focal ischemia (PMID: 28255762) and neurotrophin modulation in global ischemia (PMID: 22295573), plus Russian clinical use in acute-phase stroke (PMID: 11517472) and in early and late rehabilitation-phase stroke (PMID: 29798983). The amidate's retention of any of this activity is untested.
- **BDNF/NGF Upregulation** (evidence: preliminary): Semax raises BDNF mRNA in rat hippocampus, frontal cortex, and basal forebrain within hours, with expression changes lasting 24-48 hours (PMID: 14556513), and raised plasma BDNF in stroke patients on 10-day courses (PMID: 29798983). Neurotrophic upregulation is the effect most often cited for the amidate, and it remains a parent-compound finding.
- **Extended Duration Over Semax (Design Goal)** (evidence: preliminary): The sole engineering premise of the analog is longer molecular survival from the two end caps. No serum stability, half-life, or duration-of-effect comparison between Semax and its acetyl-amidate has been published, so the defining claimed advantage of the analog is also its least verified one.

## Research Applications

- Cognitive Research
- Neuropharmacology
- Stroke Recovery Research
- Peptide Medicinal Chemistry

## Key Studies

### Effectiveness of semax in acute period of hemispheric ischemic stroke (a clinical and electrophysiological study)

Gusev EI, Skvortsova VI, et al. — *Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova* (1997) — [PMID 11517472](https://pubmed.ncbi.nlm.nih.gov/11517472/)

The foundational clinical study of parent Semax: 30 acute hemispheric ischemic stroke patients received Semax (most effective daily doses 12 mg for moderate and 18 mg for severe strokes, over 5-10 day courses) and were compared with 80 matched controls on conventional therapy, tracked with clinical scales, EEG mapping, and somatosensory evoked potentials. The investigators reported faster restoration of damaged neurological functions with Semax. It documents the parent peptide's acute-stroke use, not the amidate analog.

### The efficacy of semax in the treatment of patients at different stages of ischemic stroke

Gusev EI, Martynov MY, et al. — *Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova* (2018) — [PMID 29798983](https://pubmed.ncbi.nlm.nih.gov/29798983/) | [doi:10.17116/jnevro20181183261-68](https://doi.org/10.17116/jnevro20181183261-68)

In 110 ischemic stroke patients split into early and late rehabilitation groups, Semax (two 10-day courses of 6000 mcg/day) raised plasma BDNF regardless of rehabilitation timing, and higher BDNF correlated with better Barthel index outcomes. It is the largest human study linking Semax administration to a neurotrophic biomarker, and the strongest clinical anchor behind neurotrophic claims for any Semax derivative.

### Effects of Semax on the Default Mode Network of the Brain

Lebedeva IS, Panikratova YR, et al. — *Bulletin of Experimental Biology and Medicine* (2018) — [PMID 30225715](https://pubmed.ncbi.nlm.nih.gov/30225715/)

In this placebo-controlled study, 24 healthy volunteers underwent resting-state fMRI before and 5 and 20 minutes after intranasal 1% Semax (14 subjects) or placebo (10 subjects). The Semax group showed a greater volume of the default mode network's rostral subcomponent in medial frontal cortex, direct human evidence that a single intranasal Semax dose engages large-scale brain networks within minutes.

### Semax, an analog of ACTH(4-7), regulates expression of immune response genes during ischemic brain injury in rats

Medvedeva EV, Dmitrieva VG, et al. — *Molecular Genetics and Genomics* (2017) — [PMID 28255762](https://pubmed.ncbi.nlm.nih.gov/28255762/)

Transcriptomic profiling of rat brain after focal cerebral ischemia showed that Semax regulates genes involved in inflammatory response, immune cell activation, and vascular remodeling, suppressing pro-inflammatory programs while upregulating protective ones. It expanded the Semax mechanism beyond neurotrophins to the neuroinflammatory cascade that drives secondary damage after stroke.

### The effect of semax and its C-end peptide PGP on expression of the neurotrophins and their receptors in the rat brain during incomplete global ischemia

Stavchansky VV, Tvorogova TV, et al. — *Molekuliarnaia Biologiia (Moskva)* (2011) — [PMID 22295573](https://pubmed.ncbi.nlm.nih.gov/22295573/)

This study compared Semax with its C-terminal Pro-Gly-Pro fragment in a rat incomplete global ischemia model and found both regulate neurotrophin and neurotrophin-receptor expression, showing the PGP tail itself is bioactive. It is directly relevant to the amidate question: capping or modifying that C-terminal region could alter a pharmacologically active part of the molecule, an interaction no study of the analog has examined.

## Frequently Asked Questions

### What is N-Acetyl Semax Amidate?

It is Semax (Met-Glu-His-Phe-Pro-Gly-Pro) with an acetyl group capping the N-terminus and an amide capping the C-terminus, written Ac-MEHFPGP-NH2. The structure is authoritatively registered in PubChem (CID 172638603; C39H54N10O10S; 855.0 g/mol; CAS 2920938-90-3). It is sold as a research chemical and has no published experimental literature.

### Is N-Acetyl Semax Amidate stronger or longer-lasting than Semax?

Unknown. The end caps are designed to resist the exopeptidases that clear Semax from plasma in about 2-3 minutes, so longer molecular survival is a reasonable hypothesis, but no serum stability assay, half-life measurement, or potency comparison of the analog has been published. Claims of superior strength or duration are vendor extrapolations.

### Has N-Acetyl Semax Amidate been studied in humans?

No. All human data in this space belongs to unmodified Semax: Russian stroke studies including a 110-patient series, and a placebo-controlled fMRI study in 24 healthy volunteers. None of it administered the acetyl-amidate, and results from the parent cannot be assumed to transfer to a chemically distinct analog.

### What is the difference between Adamax and N-Acetyl Semax Amidate?

Both are unofficial Semax derivatives with the same N-acetyl cap. The amidate stops there, adding only the C-terminal amide, while Adamax attaches a bulky lipophilic adamantane cage at the C-terminus instead. The amidate's structure is registered in PubChem; Adamax has no authoritative registry entry. Neither has any published experimental study.

### Is N-Acetyl Semax Amidate approved anywhere?

No. Semax is a registered drug in Russia and Ukraine, but the registration covers only the unmodified peptide. The amidate is an unapproved research chemical in every jurisdiction, and human use would be uncontrolled self-experimentation with an untested analog.

## Related Peptides

- [Semax](https://peptpedia.org/peptide/semax)
- [Adamax](https://peptpedia.org/peptide/adamax)
- [Adalank](https://peptpedia.org/peptide/adalank)
- [Selank](https://peptpedia.org/peptide/selank)

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This content is for educational and research purposes only. It is not medical advice, and the compounds covered are research chemicals not approved for human use unless explicitly stated otherwise.

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