AXON

Semax: Cognitive Neuropeptide Research Guide

A synthetic heptapeptide (MEHFPGP) derived from the ACTH(4-7) fragment — studied for BDNF and NGF upregulation, dopaminergic modulation, and neuroprotective mechanisms in preclinical models.

Sequence MEHFPGP
Parent Compound ACTH(4-7)
Market Avg $84
Sub-Line AXON
Research Updated April 2026

What Is Semax?

Semax is a synthetic heptapeptide analogue of ACTH(4-10) with the sequence Met-Glu-His-Phe-Pro-Gly-Pro, primarily studied for BDNF upregulation, neuroprotection, stroke recovery, and cognitive enhancement.

Semax is a synthetic heptapeptide with the amino acid sequence Met-Glu-His-Phe-Pro-Gly-Pro (MEHFPGP), developed at the Institute of Molecular Genetics (IMG) of the Soviet Academy of Sciences and patented in 1982. The compound is structurally based on the 4–7 fragment of adrenocorticotropic hormone (ACTH), combined with C-terminal Pro-Gly-Pro extension to enhance enzymatic stability and blood-brain barrier penetrance compared to the native ACTH fragment. Semax was developed as part of a broader Soviet and Russian research programme into neuropeptide pharmacology that also produced Selank.

Unlike full-chain ACTH (which comprises 39 amino acids and potently stimulates the adrenal cortex to produce cortisol), Semax contains only the ACTH(4-7) core — the region responsible for behavioural and neurotrophic effects — without the N-terminal and C-terminal sequences required for adrenal steroidogenesis. This means Semax research does not involve cortisol elevation or HPA axis activation, allowing for cleaner investigation of the ACTH fragment's CNS-specific biology. Semax has been registered as a pharmaceutical agent in Russia under the brand name Semax (Семакс) for neurological applications, but has not received regulatory approval in Western jurisdictions.

In research contexts, Semax is studied for its remarkable ability to upregulate neurotrophic factors — particularly BDNF (brain-derived neurotrophic factor) and NGF (nerve growth factor) — at concentrations relevant to preclinical models. These neurotrophins are central to synaptic plasticity, neuronal survival, and cognitive function, making Semax an important research tool for studying neuroprotective mechanisms and cognitive biology. All Semax supplied by Rainbow Peptide is provided exclusively for qualified laboratory research use and carries no approval for human administration.

Mechanism of Action

Semax drives BDNF and NGF expression in cortical and hippocampal tissue, activates ACTH receptors for neuroprotection, and enhances dopamine/serotonin turnover — making it unique among nootropic peptides for its direct neurotrophic action.

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    BDNF and NGF Upregulation

    The most extensively documented mechanism of Semax in preclinical research is upregulation of BDNF (brain-derived neurotrophic factor) and NGF (nerve growth factor) in hippocampal, cortical, and striatal brain regions. BDNF is a master regulator of long-term potentiation (LTP), synaptic plasticity, and neurogenesis in the adult brain. Studies show Semax induces peak BDNF upregulation at 1–3 hours post-administration in rat models, with expression returning to baseline by 24 hours.

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    Dopaminergic and Serotonergic Modulation

    Research has characterised Semax's effects on monoaminergic neurotransmitter systems. In the nigrostriatal and mesocortical dopamine pathways, Semax administration has been associated with increased dopamine turnover and enhanced D1/D2 receptor sensitivity. Serotonergic effects include increased 5-HT release in the frontal cortex, which may contribute to the attentional and mood-stabilising dimensions of Semax's research profile.

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    VEGF-Mediated Neuroprotection

    Semax has been shown to upregulate vascular endothelial growth factor (VEGF) expression in CNS tissue following ischaemic injury models. VEGF promotes angiogenesis and also has direct neuroprotective effects — stimulating neuronal survival via VEGFR2-PI3K-AKT signalling independent of vascular effects. This mechanism positions Semax research at the intersection of neuroprotection and cerebrovascular biology.

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    Melanocortin Receptor Partial Agonism

    As a structural derivative of the ACTH(4-7) sequence, Semax retains partial agonist activity at melanocortin receptors — particularly MC4R, which is expressed widely in the brain. MC4R activation has been linked to cognitive enhancement, appetite regulation, and neuroprotective signalling. This receptor interaction is considered a primary upstream mechanism for many of Semax's CNS effects.

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    Anti-Inflammatory and Anti-Apoptotic Gene Expression

    Transcriptomic studies of Semax-treated rodent brain tissue have identified upregulation of anti-apoptotic genes (Bcl-2 family members) and downregulation of pro-inflammatory markers (COX-2, iNOS) in peri-ischaemic tissue. These expression changes correlate with reduced lesion volumes and improved functional recovery scores in stroke model animals, supporting neuroprotective research applications.

Key Research Findings

2001

BDNF Upregulation and Memory Enhancement

Grigoriev et al. demonstrated that Semax administration in healthy rats produced significant increases in BDNF expression in the hippocampus and frontal cortex, correlating with improved spatial memory performance in the Morris water maze at 48-hour and 7-day intervals post-training. The BDNF increase preceded and predicted the behavioural improvement, establishing neurotrophic factor induction as a key mechanism.

Grigoriev VV et al. — Psychopharmacology, 2001
2008

Neuroprotection in Stroke Models

In rat middle cerebral artery occlusion (MCAO) stroke models, Semax administration at reperfusion reduced infarct volume by approximately 40% compared to vehicle controls at 24 hours. Treated animals also showed significantly better neurological deficit scores and reduced cerebral oedema. Mechanistic analysis identified VEGF upregulation and anti-apoptotic gene expression as primary contributors to the neuroprotective effect.

Miasoedov NF et al. — J Neurosci Res, 2008
2014

Cognitive Enhancement in Hypoxia Models

Research investigating Semax under hypoxic conditions found that pretreatment significantly preserved cognitive performance in rodents subjected to acute normobaric hypoxia — a model relevant to altitude physiology and cerebral blood flow research. Semax-treated animals maintained spatial orientation and conditional reflex performance at oxygen levels where controls showed significant impairment, highlighting VEGF-driven neuroprotection as a key mechanism.

Antonova LV et al. — Neuropeptides, 2014
2018

Gene Expression Profiling in Rat Brain

A comprehensive transcriptomic analysis of Semax's effects on rat brain gene expression identified 84 differentially expressed genes following a single dose. Upregulated pathways included immediate-early gene response (c-Fos, Arc), BDNF-TrkB signalling cascade, and MAP kinase-ERK1/2 activation. Downregulated gene clusters included inflammatory response and oxidative stress pathways, providing a genomic framework for interpreting Semax's broad neuroprotective profile.

Stavchansky VV et al. — Cell Mol Neurobiol, 2018

Reconstitution Reference

The following reference is provided for licensed research professionals only. All reconstitution must comply with your institution's biosafety protocols.

Vial Size BAC Water Volume Resulting Concentration Storage Peptide Calculator
5 mg 2.0 mL 2,500 mcg/mL 2–8°C, use within 28 days Calculate Dose →

Semax lyophilised powder is highly water-soluble. Reconstitute with bacteriostatic water only. Store lyophilised powder at -20°C away from light. Do not use if solution appears cloudy or discoloured after reconstitution.

Competitive Pricing Comparison

Market price data from independent competitor analysis. All products are For Research Use Only.

Supplier Price Range (per vial) Avg Market Price COA Available
Competitor Low $60 — Varies
Competitor High $130 — Varies
Market Average — $84 —
Rainbow Peptide View Price → ✓ Yes — HPLC + MS

Research Semax

View our Semax research compound specification, certificate of analysis, and current pricing for qualified research applications.

View Semax Product → Peptide Calculator

For Research Use Only. Not for human consumption.

Frequently Asked Questions

What is Semax?

Semax is a synthetic heptapeptide (Met-Glu-His-Phe-Pro-Gly-Pro) derived from the ACTH(4-7) fragment of adrenocorticotropic hormone, patented in 1982 at the Institute of Molecular Genetics. It is used in research contexts studying BDNF expression, neuroprotection, and cognitive pathway biology. For Research Use Only.

How does Semax differ from ACTH?

Semax is derived from only the 4-7 fragment of ACTH, not the full 39 amino acid hormone. Unlike full ACTH, Semax does not stimulate cortisol or adrenal steroid synthesis, instead retaining the neurotrophic signalling properties of the ACTH fragment without systemic endocrine effects.

What neurotrophic factors does Semax research involve?

Semax research has documented upregulation of BDNF, NGF, and VEGF in rodent central nervous system models. BDNF upregulation is particularly well-documented in hippocampal tissue following Semax administration, with peak expression at 1–3 hours post-dose.

How is Semax reconstituted for research?

A standard 5mg vial of Semax is reconstituted with 2mL bacteriostatic water to yield a concentration of 2,500 mcg/mL. Store reconstituted Semax at 2–8°C and use within 28 days.

Is Semax approved for clinical use?

Semax is registered as a pharmaceutical product in Russia for neurological indications, but is not approved by the FDA, EMA, or TGA. Rainbow Peptide supplies Semax strictly For Research Use Only — not for human or veterinary administration.

Published Research References

Studies cited for scientific reference. Russian clinical data refers to approved domestic use — Semax is not FDA-approved. Not medical advice.

  1. Gusev EI, et al. "Neuroprotective effects of Semax in acute stroke patients." Zh Nevrol Psikhiatr Im S S Korsakova. 2005;105(3):35–41. PubMed 16052610 ↗
  2. Dmitrieva VG, et al. "Effects of the ACTH(4-7) analog Semax on the expression of BDNF and its receptor TrkB." Dokl Biochem Biophys. 2010;435:295–297. PubMed 21234742 ↗
  3. Grigoreva ME, et al. "Semax increases neuroprotective brain endogenous proopiomelanocortin peptides." Peptides. 2022;147:170687. PubMed 34743924 ↗

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