Semax

ACTH 4-7-PGP

Rank#999
CognitiveNot ApprovedApprovedPrescriptionIntranasalSubQ

Popular for:Cognitive enhancement, neuroprotection, stroke recovery

202

Total Studies

45

Human Studies

Approved

Evidence Level

Not Approved

FDA Status

Overview

Semax (Met-Glu-His-Phe-Pro-Gly-Pro) is a synthetic heptapeptide analogue of the ACTH (adrenocorticotropic hormone) fragment 4-10. Developed at the Institute of Molecular Genetics of the Russian Academy of Sciences, first described in scientific literature in 1991. It retains the melanocortin fragment (Met-Glu-His-Phe) from ACTH(4-7) with the addition of a C-terminal Pro-Gly-Pro tripeptide that protects against peptidase degradation.

Semax is approved as a prescription drug in Russia for cognitive impairment, stroke recovery, and peptic ulcer disease. Key variant: N-Acetyl Semax Amidate (NASA) has enhanced stability and potency.

Mechanism of Action

Semax increases BDNF (brain-derived neurotrophic factor) and TrkB receptor expression in the hippocampus, enhancing neuroplasticity. It modulates dopaminergic, serotonergic, and adrenergic neurotransmitter systems. Unlike full-length ACTH, Semax does NOT stimulate the adrenal cortex or raise cortisol — it acts primarily as a neuroprotective and nootropic agent. It also regulates gene expression of neurotrophins and inflammatory markers in cerebral ischemia models.

Key Research Benefits

BDNF upregulation: A single application of Semax (50 mcg/kg) significantly increased BDNF and TrkB expression in rat hippocampus, supporting neuroplasticity and memory formation (Dolotov et al., 2006, PMID: 16996037).
Neuroprotection in stroke: Demonstrated neuroprotective effects in cerebral ischemia-reperfusion models. Regulated expression of over 100 genes involved in neuronal survival and inflammation (Dergunova et al., 2020, MDPI Genes).
Cognitive enhancement: Improves memory, attention, and learning in both animal models and human clinical use (Russian clinical data). Enhances cognitive performance under stress conditions.
No adrenal stimulation: Despite being an ACTH fragment, Semax does not activate the HPA axis or raise cortisol levels, eliminating adrenal side effects.
TBI and neurological recovery: Used clinically in Russia for traumatic brain injury rehabilitation and post-stroke cognitive recovery.

Clinical Evidence Summary

Research Pipeline

Preclinical
Animal
Phase I
Phase II
Phase III
Approved

International Regulatory Status

🇷🇺
RussiaApproved1996(Semax)

Cognitive disorders, stroke recovery, peptic ulcer treatment

Source

202

Total Studies

45

Human Studies

- Dolotov et al. (2006) — 'Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus.' Single application increased BDNF expression (PMID: 16996037).

- Dergunova et al. (2020) — 'Novel Insights into the Protective Properties of ACTH(4-7)PGP (Semax) Peptide at the Transcriptome Level Following Cerebral Ischaemia-Reperfusion in Rats.' Identified comprehensive neuroprotective gene expression changes (MDPI Genes 11(6):681).

- Multiple Russian clinical studies supporting use in stroke rehabilitation and cognitive impairment (published primarily in Russian-language journals).

- **Limitation: **Like Selank, most clinical data originates from Russian institutions. Limited Western peer-reviewed replication. No Western-standard Phase III trials.

Key Studies / PubMed References

202 studies found on PubMed · showing top 25 by relevance

View all on PubMed

Therapeutic Peptides in Orthopaedics: Applications, Challenges, and Future Directions.

Review

Rahman OF, Lee SJ, Seeds WA · Journal of the American Academy of Orthopaedic Surgeons. Global research & reviews · 2026

PMID: 41490200

Semax, a Copper Chelator Peptide, Decreases the Cu(II)-Catalyzed ROS Production and Cytotoxicity of aβ by Metal Ion Stripping and Redox Silencing.

In Vitro

Tomasello MF, Di Rosa MC, Naletova I, et al. · Bioinorganic chemistry and applications · 2025

PMID: 40496623

Semax peptide targets the μ opioid receptor gene Oprm1 to promote deubiquitination and functional recovery after spinal cord injury in female mice.

Animal Study

Liu R, Chen Y, Huang H, et al. · British journal of pharmacology · 2025

PMID: 40692165

ACTH-like Peptides Compensate Rat Brain Gene Expression Profile Disrupted by Ischemia a Day After Experimental Stroke.

Animal Study

Filippenkov IB, Shpetko YY, Stavchansky VV, et al. · Biomedicines · 2024

PMID: 39767736

Semax, synthetic ACTH(4-10) analogue, attenuates behavioural and neurochemical alterations following early-life fluvoxamine exposure in white rats.

Animal Study

Glazova NY, Manchenko DM, Volodina MA, et al. · Neuropeptides · 2021

PMID: 33418449

Side Effects & Safety

Common: Generally very well tolerated. Some users report mild nasal irritation (intranasal route), slight headache at higher doses, or mild irritability/restlessness.
Rare: No serious adverse effects reported in available literature. Hair loss has been anecdotally reported by some users at higher doses (unconfirmed in clinical data).
Contraindications: Pregnancy, lactation. Caution in patients with anxiety disorders (may increase stimulation). Use with care alongside stimulant medications.
Drug interactions: May interact with dopaminergic and serotonergic drugs. Use caution with stimulants, SSRIs, and MAOIs.

Known Interactions

No curated interaction entry is live for Semax yet.

Until the interaction table is fully populated, use the interaction checker and related peptides below to explore adjacent compounds and likely research pairings.

Frequently Asked Questions

Research Disclaimer

This page is for research and educational purposes only. The information presented is based on published scientific literature and does not constitute medical advice, diagnosis, or treatment recommendations. Semax is not approved by the FDA for human therapeutic use. Always consult a qualified healthcare professional before making any health-related decisions. The studies referenced are linked to their original PubMed sources for verification.