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Semax

From PeptidePlaza, the free peptide reference · Entry #014 · Nootropic · Hand-curated entry · Editorial standards

Research warning. Approved medication in Russia; investigational in most countries. May transiently elevate blood pressure at high doses.

Semax (also known as ACTH 4-7 PGP, Семакс) is a nootropic research peptide. A synthetic analog of a fragment of ACTH that lacks hormonal activity but retains potent neuroprotective and cognitive-enhancing properties. Widely used in Russian clinical settings for stroke, memory, and attention disorders.

Semax (Met-Glu-His-Phe-Pro-Gly-Pro) is a synthetic heptapeptide analog of the 4-7 fragment of adrenocorticotropic hormone (ACTH) with a Pro-Gly-Pro extension for stability. Unlike ACTH, it has no adrenocortical activity. It is approved in Russia for treatment of stroke, TBI, and cognitive disorders. Research demonstrates potent upregulation of BDNF and NGF, activation of serotonin and dopamine systems, neuroprotection against ischemic damage, and enhancement of attention and working memory. It also exhibits anti-inflammatory effects in the CNS.

1 Mechanism of action

Rapidly increases BDNF and NGF synthesis. Activates melanocortin receptors (MC4R) without cortisol axis effects. Modulates dopaminergic and serotonergic transmission. Anti-inflammatory via inhibition of NF-κB and IL-1β.

Primary targets: MC4R · BDNF/TrkB pathway · NGF/TrkA pathway

2 Reported effects

Effects below are those reported in the published literature cited on this page. They are not claims of clinical benefit and not medical advice.

2.1 Reported benefits

  • Upregulates BDNF and NGF for neuroprotection
  • Cognitive enhancement and improved stroke recovery
  • Anti-inflammatory effects in the central nervous system

2.2 Side effects

  • Nasal irritation with intranasal delivery
  • Mild agitation or restlessness at high doses
  • Headache reported in some clinical studies

3 Chemical and physical properties

CAS number80714-61-0
Molar mass813.94 g/mol
Purity (typical)>99.0%
Half-life~minutes (rapid enzymatic degradation; intranasal use)
Storage−20 °C, lyophilised powder, desiccated
SolubilitySterile water / bacteriostatic water
Receptors / targetsMC4R, BDNF/TrkB pathway, NGF/TrkA pathway

3.1 Amino acid sequence

Met-Glu-His-Phe-Pro-Gly-Pro

4 Research dosages

0.1% intranasal solution 1–2 drops 2–3x daily; 1–5 mg SC in research protocols.

Dosages are reported from published protocols for reference only. Research chemicals are not for human consumption.

5 Research studies (8)

  1. Semax, an ACTH Analog with Nootropic Properties: Review
    CNS Drug Reviews (2002) · Review · N/A (review)
    Comprehensive review of Semax pharmacology. Covers neuroprotective effects, BDNF/NGF upregulation, cognitive enhancement, and clinical use in Russian medicine.
    Key finding: Semax upregulates BDNF 2–4x and NGF 1.5–2x in hippocampal neurons — mechanism for neuroprotection and cognitive enhancement.
  2. Effect of Semax on Stroke Recovery: Randomized Clinical Trial
    Cerebrovascular Diseases (2001) · RCT · N=110
    Semax improved neurological outcomes and cognitive recovery post-ischemic stroke in a Russian RCT; significant reduction in deficit scores vs placebo.
    Key finding: Significant improvement in neurological deficit scores post-stroke vs placebo — basis for Russian clinical approval.
  3. The Potential of the Peptide Drug Semax and Its Derivative for Correcting Pathological Impairments in the Animal Model of Alzheimer's Disease
    Acta naturae (2025) · Preclinical
    Copyright ® 2025 National Research University Higher School of Economics.
  4. The Effect of Peptide Semax, an ACTH(4-10) Analogue, on Intracellular Calcium Dynamics in Rat Brain Neurons
    Bulletin of experimental biology and medicine (2025) · Preclinical
    Springer Science+Business Media, LLC, part of Springer Nature.
  5. Semax peptide targets the μ opioid receptor gene Oprm1 to promote deubiquitination and functional recovery after spinal cord injury in female mice
    British journal of pharmacology (2025) · Preclinical
    CONCLUSION AND IMPLICATIONS: Semax promoted SCI functional recovery by targeting μ-opioid receptors, which regulated USP18 and, subsequently, deubiquitination of the fat mass and obesity-associated protein (FTO), suggesting its potential for SCI treatment.
  6. Semax, a Copper Chelator Peptide, Decreases the Cu(II)-Catalyzed ROS Production and Cytotoxicity of aβ by Metal Ion Stripping and Redox Silencing
    Bioinorganic chemistry and applications (2025) · Preclinical
    Bioinorganic Chemistry and Applications published by John Wiley & Sons Ltd.
  7. Antidepressant-like and antistress effects of the ACTH(4-10) synthetic analogs Semax and Melanotan II on male rats in a model of chronic unpredictable stress
    European journal of pharmacology (2024) · Preclinical
    The results support the argument that ACTH(4-10) analogs and other noncorticotropic melanocortins may have promising therapeutic potential for the treatment and prevention of depression and other stress-related pathologies.
  8. Semax, a Synthetic Regulatory Peptide, Affects Copper-Induced Abeta Aggregation and Amyloid Formation in Artificial Membrane Models
    ACS chemical neuroscience (2022) · Preclinical
    The results suggest that Semax inhibits fiber formation by interfering with the fibrillogenesis of Aβ:Cu2+ complexes.

6 Safety and risk profile

6.1 Regulatory status

Semax is currently classified as Phase 3 clinical trials. It has no approved human indication in the United States; availability elsewhere does not imply demonstrated safety or efficacy.

Safety score: 55/100 — moderate concern. Derived from clinical data volume, known risks and regulatory status.

6.2 Contraindications

Conditions and populations in which use is contraindicated:

  • Acute anxiety or agitation disorders
  • Uncontrolled hypertension
  • Pregnancy (insufficient safety data)
  • History of seizures

6.3 Drug interactions

Drug or classInteractionRisk
MAOIs / stimulant medicationsAdditive dopaminergic effects possible — monitor for overstimulation.Moderate
AntihypertensivesMild BP elevation at high doses may counteract antihypertensives.Low

6.4 Long-term risks

  • Neurotrophin receptor desensitization with chronic use
  • Unknown long-term effects of sustained BDNF/NGF elevation
  • Limited Western safety data beyond Russian clinical experience

6.5 Research best practices

  • Store at −20 °C; intranasal formulations should be refrigerated
  • Administer intranasally for optimal CNS penetration
  • Cycle usage (4–6 weeks on / 2–4 weeks off) to prevent tachyphylaxis
Safety data disclaimer. Safety assessments are based on published literature and are for educational reference only. Clinical evidence varies significantly between peptides. Always consult primary research and current regulatory guidance.

7 Frequently asked questions

How does Semax differ from other cognitive enhancers?
Semax uniquely combines neuroprotection (via BDNF/NGF upregulation) with cognitive enhancement (via dopamine/serotonin modulation) — simultaneously protecting neurons while improving function. It is approved as a medication in Russia for stroke recovery and cognitive disorders.
What is the regulatory status of Semax?
Semax is approved as a medication in Russia and several CIS countries for treatment of stroke, TBI, and cognitive disorders. It is available as a 0.1% intranasal solution. It is not FDA-approved and is considered investigational in Western countries.

8 References

  1. The Potential of the Peptide Drug Semax and Its Derivative for Correcting Pathological Impairments in the Animal Model of Alzheimer's Disease PubMed (2025). Radchenko AI, et al.. View source
  2. The Effect of Peptide Semax, an ACTH(4-10) Analogue, on Intracellular Calcium Dynamics in Rat Brain Neurons PubMed (2025). Kolbaev SN, et al.. View source
  3. Semax peptide targets the μ opioid receptor gene Oprm1 to promote deubiquitination and functional recovery after spinal cord injury in female mice PubMed (2025). Liu R, et al.. View source
  4. Genes That Associated with Action of ACTH-like Peptides with Neuroprotective Potential in Rat Brain Regions with Different Degrees of Ischemic Damage PubMed (2025). Filippenkov IB, et al.. View source

Related compounds

Entries that share a target, a mechanism, or a research area with Semax.

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Melanotan IInootropic

Also targets MC4R

A potent cyclic analog of α-MSH that activates melanocortin receptors broadly. Studied for UV-independent melanogenesis, appetite suppression, and as the parent compound of PT-141 (Bremelanotide).

Selanknootropic

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DSIPnootropic

Shares modulates and axis pharmacology

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GHK-Cuanti-aging

Shares activates and synthesis pharmacology

A naturally occurring tripeptide-copper complex found in human plasma, saliva, and urine. Plasma levels decline sharply with age. Extensively studied for collagen induction, skin remodeling, and gene expression regulation.

KPVrecovery

Shares pathway and il-1 pharmacology

Three amino acids clipped from the tail of α-MSH — small enough to ride the PepT1 transporter directly into intestinal cells, where it shuts down NF-κB signalling.

9 See also

For research reference only. Not medical advice. Peptides may be regulated or restricted in your jurisdiction. Entry validated by the PeptidePlaza Biomedical Research Desk; see editorial standards.

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