NA-Semax-Amidate

NA-Semax-Amidate (Ac-Met-Glu-His-Phe-Pro-Gly-Pro-NH2) is a synthetic heptapeptide analog of the adrenocorticotropic hormone fragment ACTH(4-10), extended by a C-terminal Pro-Gly-Pro tripeptide that abolishes hormonal melanocortin receptor binding. It differs from its parent compound Semax by two terminal chemical modifications: N-terminal acetylation and C-terminal amidation.

The acetyl group on the N-terminus shields the peptide from leucine aminopeptidase cleavage, while C-terminal amidation blocks carboxypeptidase-mediated degradation. Together these modifications are expected to extend metabolic half-life relative to unmodified Semax, whose plasma half-life after intranasal dosing is on the order of minutes. No formal pharmacokinetic study has been published specifically for NA-Semax-Amidate.

The principal proposed mechanism involves upregulation of brain-derived neurotrophic factor (BDNF) and its receptor TrkB in the hippocampus, established for Semax in rat models. Semax also suppresses pro-inflammatory pJNK signaling and MMP-9 expression, and upregulates the neuroprotective transcription factor pCREB, as demonstrated in ischemia-reperfusion models. Modulation of serotonin, dopamine, and enkephalin (opioid) signaling pathways is proposed based on behavioral pharmacology data but has not been characterized at the receptor level for this specific analog.

No published human or animal clinical trials have been conducted specifically on NA-Semax-Amidate. All evidence is extrapolated from the parent compound Semax, which carries regulatory approval only in Russia and Ukraine for ischemic stroke and cognitive disorders.

In the most informative human study (Gusev et al., Zh Nevrol Psikhiatr Im S S Korsakova 2018, PMID 29798983, n=110), post-stroke patients received intranasal Semax at 6,000 mcg/day in two 10-day courses separated by a 20-day interval. Semax administration elevated plasma BDNF throughout the study period, accelerated improvement on the Barthel index of functional independence, and improved motor scores on the British Medical Research Council scale regardless of rehabilitation timing.

Preclinical work by Dolotov et al. (Brain Research 2006, PMID 16996037) demonstrated that a single intranasal Semax dose of 50 µg/kg in rats produced a 1.4-fold increase in hippocampal BDNF protein, a 1.6-fold increase in TrkB tyrosine phosphorylation, and 3-fold and 2-fold increases in BDNF and TrkB mRNA, respectively, alongside improved conditioned avoidance learning.

A 2021 rat tMCAO study (PMID 34201112, DOI 10.3390/ijms22126179, n=5-7 per group) found that Semax at 100 µg/kg reduced pJNK by more than 1.5-fold, decreased MMP-9 and c-Fos, and elevated pCREB in peri-infarct cortex. A small study of 16 fatigued healthy volunteers reported improved memory test accuracy after a single Semax dose; sample size precludes generalizable conclusions. No Phase 2 or Phase 3 trials for any Semax variant have been published in the Western peer-reviewed literature, and evidence specific to NA-Semax-Amidate remains anecdotal.

Typical dosage: 300-600 mcg (daily).

No established clinical dosing regimen exists for NA-Semax-Amidate. The following reflects community-reported protocols inferred from approved Semax dosing and adjusted downward under the assumption that dual terminal modifications confer greater per-microgram potency. This assumption lacks controlled clinical validation.

Intranasal: Community protocols most commonly cite 100 to 300 mcg once or twice daily. A starting dose of 100 to 200 mcg once daily with optional titration to 300 mcg per dose is the most frequently reported pattern. Formulations are typically 0.1% (approximately 100 mcg per 100 µL actuation) or 0.3% solutions. A cycle length of 10 to 30 days with an equal washout period is standard in community use.

Subcutaneous injection: Anecdotal protocols describe 200 to 500 mcg once daily for cycles of 10 to 30 days.

For reference only, approved Semax nasal spray dosing in Russia ranges from 200 to 600 mcg twice daily for cognitive impairment up to 2,000 to 4,000 mcg three to six times daily for acute stroke under medical supervision.

This information is provided for educational and scientific reference only and does not constitute medical advice. NA-Semax-Amidate is not approved by any regulatory authority and is classified as a research chemical in most jurisdictions outside Russia.

No compound-specific stability data has been identified for this peptide. The general lyophilized-peptide handling framework applies — see Storage & handling for temperature, reconstitution diluent, and beyond-use dating principles.

Combination use of NA-Semax-Amidate with other compounds has not been examined in any controlled published study. All reported combinations are anecdotal, originating from self-reports in online research communities.

• Selank: The most commonly cited pairing. Selank is a Russian synthetic peptide analog of tuftsin studied for anxiolytic and serotonergic properties. Community users report it may mitigate the mild stimulatory or anxiogenic effects sometimes attributed to Semax analogs while providing complementary anxiolytic coverage. No controlled data support this combination.

• BPC-157: Occasionally reported in combination for theorized complementary neuroprotective and gut-brain axis effects. Evidence is entirely anecdotal.

• NAD+ precursors (NMN, NR): Some community users report combining these for theorized mitochondrial and neuroplasticity synergy. No published evidence supports this pairing.

All combination strategies described here are anecdotal only and should be treated as such.

NA-Semax-Amidate is not currently FDA-approved for any indication. Effective April 22, 2026, the FDA removed NA-Semax-Amidate from Category 2 of its Section 503A bulk drug substances list after the original nominators withdrew their nominations. This removal lifts the prior “significant safety risk” designation but does not place NA-Semax-Amidate on the 503A Bulks List. Compounding pharmacies may prepare it with a valid physician prescription and pharmaceutical-grade API from an FDA-registered manufacturer. The FDA’s Pharmacy Compounding Advisory Committee (PCAC) is scheduled to review this substance at its July 23–24, 2026 public meeting. Removed from FDA Category 2 effective April 22, 2026. Selected for PCAC review Day 2 — July 24, 2026. PCAC agenda: DSIP (Emideltide), Semax, Epitalon. NOT currently on 503A Bulks List — requires physician Rx. Source: FDA Advisory Committee Calendar / Lengea Law, May 2026.

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Reported side effects: Well-tolerated, potential overstimulation

Published safety data specific to NA-Semax-Amidate do not exist. The following is extrapolated from studies of unmodified Semax.

Intranasal Semax at doses of 600 to 12,000 mcg/day for up to 30 consecutive days has been used in Russian clinical studies without reported serious adverse events. Documented or frequently reported effects include:

• Nasal and throat irritation; transient changes in smell or taste with intranasal administration, reported in approximately 10% of subjects in some accounts • Mild stimulatory effects; a 1996 behavioral study noted an anxiogenic component in Semax pharmacology and cautioned against use in individuals with pre-existing anxiety disorders • Headache, insomnia, and mild nausea reported in community use but not systematically documented in clinical trials • Elevated blood glucose reported anecdotally in users with diabetes • Injection site reactions including pain, erythema, and swelling with subcutaneous administration

The N-acetyl and C-amidate modifications have not been associated with distinct new toxicity compared to Semax in any published report; however, NA-Semax-Amidate-specific safety data are absent and additional adverse effects cannot be excluded. Semax and its analogs have not been studied in pregnancy, lactation, or severe hepatic or renal impairment; use is not recommended in these populations. No long-term safety data exist for any Semax variant beyond approved short-course clinical use in Russia.