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ACTH(4-10)-derived heptapeptide (Russian regulator peptide school)

Semax

Met-Glu-His-Phe-Pro-Gly-Pro — a synthetic heptapeptide analogue of the ACTH(4-10) neuropeptide fragment with a Pro-Gly-Pro C-terminal stability extension

Early Human EvidenceEstablished clinical useLast updated 2026-07-20
Overview

Semax is the older sibling of Selank in the Russian regulator-peptide tradition. Registered in Russia since 1994, it is one of the earliest fruits of the Institute of Molecular Genetics of the Russian Academy of Sciences' peptide programme. The design strategy is the same one that produced Selank: take a naturally occurring bioactive peptide fragment, extend it at the C-terminus with a Pro-Gly-Pro tail that greatly increases stability, and deliver it intranasally to bypass first-pass metabolism. In Semax's case the parent sequence is the ACTH(4-10) fragment — the portion of adrenocorticotropic hormone that carries neuromodulatory activity in the brain without the peripheral corticotropic (adrenal-stimulating) activity of the full hormone. That is the design premise: keep the brain effects, drop the endocrine effects.

Chemically, Semax is Met-Glu-His-Phe-Pro-Gly-Pro. The Met-Glu-His-Phe portion is the ACTH(4-7) sequence proper; the -Pro-Gly-Pro C-terminal extension is what turns it into a stable, centrally-active pharmaceutical. Intranasal delivery of the 0.1% solution reaches central concentrations sufficient to produce cognitive and neuroprotective effects; the 1% solution is used in acute stroke where the requirement is a rapid neuroprotective effect during the ischaemic window.

The Russian approved uses are broad and reflect the compound's polypharmacological profile. Acute ischaemic stroke (Semax 1% administered in the emergency-department window) and transient ischaemic attack are the acute indications. Chronic discirculatory encephalopathy, cognitive impairment, optic nerve atrophy and chronic fatigue are the chronic indications. Semax has also been used in Russian paediatric practice for attention-deficit and other neurodevelopmental conditions. Gusev and Skvortsova's stroke work (Moscow, 2005 and 2013) is the pivotal clinical evidence for the acute-stroke registration; the mechanistic Institute of Molecular Genetics literature covers the BDNF/NGF and neuroprotective story.

For Western readers, Semax occupies the same regulatory-geography position as Selank: it is a real approved medicine in Russia and some CIS countries, invisible in Western regulatory frameworks, with published evidence dominated by Russian-language sources. Grey-market lyophilized Semax vials circulate in the peptide-therapy market for reconstitution as intranasal or subcutaneous formulations. These are the same peptide but not the same regulated product as Russian Semax.

Quick Facts & Evidence
Category
ACTH(4-10)-derived heptapeptide (Russian regulator peptide school)
Research area
Regulator peptide
Most studied for
  • Acute ischaemic stroke (Russian approved use)
  • Transient ischaemic attack and chronic ischaemic conditions
  • Cognitive impairment and mild dementia
  • Optic nerve atrophy
  • Neurodevelopmental and attention conditions (paediatric Russian use)
Clinical status
Established clinical use
Human evidence
Early Human Evidence
Regulatory status
Registered in the Russian Federation since 1994 as intranasal solutions in two strengths: Semax 0.1% for chronic use (mild cognitive impairment, discirculatory encephalopathy) and Semax 1% for acute indications (acute ischaemic stroke, transient ischaemic attack). Also registered in some CIS countries.

Early Human Evidence

Small-scale human studies, observational data, or off-label case reports only. Substantial uncertainty remains.

Research Protocols

Research Protocol Snapshot

Preparation covered on this page

Freeze-dried injectable research format

This page covers the RUO lyophilized Semax vial reconstituted with bacteriostatic water for subcutaneous research use, following the standard Healthy Mango preparation convention. The registered Russian Semax 0.1% and 1% intranasal solutions are a separate ready-to-use presentation with their own package inserts and are not covered by this Snapshot.

Semax research values at a glance.

ItemExample value
Vial size10 mg
Liquid used to mixBacteriostatic water
Amount of liquid added2.0 mL
Final concentration5 mg/mL
How it's givenSubcutaneous injection
Research dose0.3–1.0 mg (300–1000 mcg) per dose
Frequency1–2× daily (morning preferred)
After mixingRefrigerate; use within 7–10 days
Reported Dosing

The practitioner-reference research protocol for grey-market lyophilized Semax is 0.3–1.0 mg per subcutaneous dose, 1–2× daily (morning preferred), across a 4–8 week active cycle. It is educational reference, not a recommendation.

The Reported Protocol

DoseFrequencyDurationNotes
0.3–1.0 mg1–2× daily, subcutaneous (morning preferred)4–8 weeks on, 2–4 week washout0.06–0.2 mL at 5 mg/mL

Why protocols vary

The 0.3–1.0 mg per subcutaneous dose range across a 4–8 week active cycle is the practitioner-reference protocol for the grey-market RUO lyophilized preparation covered by this Snapshot.

The Russian registered Semax product is a ready-to-use intranasal solution supplied at 0.1% (chronic indications, 200–2000 μg intranasal per day) or 1% (acute stroke, 6–18 mg intranasal per day divided across the day). Those regimens are labelled for their approved indications; they are not the RUO subcutaneous research reference the Snapshot describes.

Preparing the Solution

Turning the freeze-dried powder into a measurable liquid.

Documented preparation

The documented research protocol is based on this preparation concentration.

Freeze-dried powder: 10 mg vial

Diluent: 2.0 mL bacteriostatic water

Final concentration: 5 mg/mL

Vial and volume from the practitioner reference; concentration calculated · Research-practitioner guide

Your vial

Matching preparation

Bacteriostatic water

2mL

Resulting concentration

5 mg/mL

Equivalent volume

The reported research amount of 0.30–1 mg is contained within

0.06–0.20mL

of the prepared solution now in your vial.

Show calculation
Documented concentration
10 mg ÷ 2 mL = 5 mg/mL
Bacteriostatic water to match the documented concentration
10 mg ÷ 5 mg/mL = 2 mL
Equivalent volume at this concentration
0.30–1 mg ÷ 5 mg/mL = 0.06–0.2 mL

This tool performs arithmetic conversions using the preparation example and reported research amount shown on this page. It does not recommend an amount, route, preparation method, or use.

This tool performs arithmetic conversions using the preparation example and reported research amount shown on this page. It does not recommend an amount, route, preparation method, or use.

Sources for these values

  • Documented in the practitioner referenceResearch-practitioner guide

This example explains how concentration and volume are calculated for the standard RUO preparation. It is not a preparation guide.

How It's Given

Method used for this format

Subcutaneous injection (grey-market RUO convention), 1–2× daily during an active cycle, morning preferred

Documented in the practitioner reference · Research-practitioner guide

Why this method

Semax is a seven-amino-acid peptide; the subcutaneous route delivers it into circulation without the gastrointestinal degradation that would break the molecule down.

Morning-preferred dosing follows the practitioner-reference cadence — the compound is activating and late-day dosing is not recommended. The registered Russian intranasal Semax product uses a different delivery route entirely and is a distinct presentation.

Injection sites reported

  • Abdomen (rotate sites)
  • Front of the thigh
  • Avoid scarred, bruised, inflamed, or infected skin
Storage

Before mixing

  • Refrigerate 2–8 °C
  • Protect from light
  • Do not freeze

Documented in the practitioner reference; general RUO practice · Research-practitioner guide

After mixing

  • Refrigerate 2–8 °C
  • Use within 7–10 days
  • Do not freeze
  • Discard if cloudy or discoloured

Documented in the practitioner reference · Research-practitioner guide

Handling

  • Direct diluent slowly down the vial wall
  • Gently swirl until dissolved — do not shake
  • New sterile needle each draw
  • Do not share vials

General RUO practice · Research-practitioner guide

Storage guidance summarises documented practitioner practice and standard RUO peptide handling. The registered Russian intranasal Semax product has its own package-insert storage instructions that supersede these general guidelines wherever it is dispensed. Verify the specific vial's supplied instructions before use.

Common Cycle

The practitioner-reference cadence is a 4–8 week active cycle followed by a 2–4 week washout.

Cycle Length
4–8 weeks on
Break Before the Next Cycle
2–4 week washout between cycles
What the Research Shows
Not defined for grey-market use

Documented in the practitioner reference · Research-practitioner guide

The Russian registered Semax uses defined 10–14 day chronic-indication courses (Gusev, Skvortsova) that can be repeated; the acute-stroke label uses a 3–5 day intensive course. Neither maps directly onto the grey-market SC cadence above — they are labelled regimens for a different presentation.

Compound Overview

Current areas of research

Effects reported in Russian clinical literature and approved use.

  • Neuroprotection during acute ischaemic stroke (Semax 1% in the emergency-department window)
  • Cognitive improvement in discirculatory encephalopathy and mild cognitive impairment
  • BDNF and NGF upregulation in mechanistic studies
  • Well-tolerated in decades of Russian clinical use
Mechanism of action

Semax is the older sibling of Selank in the Russian regulator-peptide tradition. Registered in Russia since 1994, it is one of the earliest fruits of the Institute of Molecular Genetics of the Russian Academy of Sciences' peptide programme. The design strategy is the same one that produced Selank: take a naturally occurring bioactive peptide fragment, extend it at the C-terminus with a Pro-Gly-Pro tail that greatly increases stability, and deliver it intranasally to bypass first-pass metabolism. In Semax's case the parent sequence is the ACTH(4-10) fragment — the portion of adrenocorticotropic hormone that carries neuromodulatory activity in the brain without the peripheral corticotropic (adrenal-stimulating) activity of the full hormone. That is the design premise: keep the brain effects, drop the endocrine effects.

Chemically, Semax is Met-Glu-His-Phe-Pro-Gly-Pro. The Met-Glu-His-Phe portion is the ACTH(4-7) sequence proper; the -Pro-Gly-Pro C-terminal extension is what turns it into a stable, centrally-active pharmaceutical. Intranasal delivery of the 0.1% solution reaches central concentrations sufficient to produce cognitive and neuroprotective effects; the 1% solution is used in acute stroke where the requirement is a rapid neuroprotective effect during the ischaemic window.

The Russian approved uses are broad and reflect the compound's polypharmacological profile. Acute ischaemic stroke (Semax 1% administered in the emergency-department window) and transient ischaemic attack are the acute indications. Chronic discirculatory encephalopathy, cognitive impairment, optic nerve atrophy and chronic fatigue are the chronic indications. Semax has also been used in Russian paediatric practice for attention-deficit and other neurodevelopmental conditions. Gusev and Skvortsova's stroke work (Moscow, 2005 and 2013) is the pivotal clinical evidence for the acute-stroke registration; the mechanistic Institute of Molecular Genetics literature covers the BDNF/NGF and neuroprotective story.

For Western readers, Semax occupies the same regulatory-geography position as Selank: it is a real approved medicine in Russia and some CIS countries, invisible in Western regulatory frameworks, with published evidence dominated by Russian-language sources. Grey-market lyophilized Semax vials circulate in the peptide-therapy market for reconstitution as intranasal or subcutaneous formulations. These are the same peptide but not the same regulated product as Russian Semax.

  • Approved neuroprotective / nootropic intranasal medicine in Russia since 1994 (0.1% for chronic use, 1% for acute stroke)
  • Heptapeptide ACTH(4-10) analogue with a Pro-Gly-Pro C-terminal stability extension — the same design strategy as Selank
  • Broad approved indication set in Russia (acute stroke, TIA, encephalopathy, cognitive impairment, optic nerve atrophy) — invisible in Western regulatory frameworks
Human research

Gusev and Skvortsova (Moscow, 2005 and 2013 follow-up) are the reference clinical publications on Semax 1% in acute ischaemic stroke. Their studies support the Russian regulatory registration of Semax as a neuroprotective adjunct during the acute stroke window.

The Myasoedov review and related Institute of Molecular Genetics publications cover the design strategy shared with Selank (Pro-Gly-Pro C-terminal extension of a naturally occurring bioactive peptide) and the mechanistic profile — BDNF and NGF upregulation, monoamine and cholinergic modulation, reduced excitotoxicity.

The chronic-indication clinical literature is spread across Russian neurological journals and covers discirculatory encephalopathy, mild cognitive impairment, optic nerve atrophy and paediatric attention conditions. It is not as well-known in Western neurology because it has not been translated into ICH-GCP randomised trials by Western sponsors.

  • Gusev / Skvortsova acute stroke

    The Moscow stroke clinical programme supporting the Russian acute ischaemic stroke registration of Semax 1% intranasal. Semax administered in the emergency-department window supported neurological recovery vs standard care.

  • Skvortsova follow-up stroke work

    Continuation and extension of the Semax stroke clinical evidence base into the 2010s.

  • Myasoedov review (shared with Selank)

    Consolidating review of the Russian regulator-peptide tradition, including Semax and Selank, by one of the original developers.

  • Russian Semax pharmaceutical registry

    The regulatory registration documentation for Semax in Russia — the document that establishes the approved-medicine identity of the compound.


Semax is an approved medicine in Russia and some CIS countries. It has no MHRA / EMA / FDA authorisation. That regulatory-geography split — a compound with a decades-long approved-medicine identity in one part of the world and no regulatory presence in another — is the primary framing consumers need to understand.

The Gusev and Skvortsova stroke work (Moscow) supports the acute-stroke registration; the broader chronic-indication evidence base and the mechanistic literature support the other approved uses. No Western sponsor has run ICH-GCP randomised placebo-controlled trials of the compound.

The Russian regulator-peptide tradition that produced Semax also produced Selank (see the related compound page) and, differently, Epitalon. Understanding one peptide from this tradition provides useful context for understanding the others.

Safety considerations

Adverse events reported in Russian clinical experience.

  • Occasional mild nasal irritation with the intranasal solution
  • Rarely transient headache or dizziness
  • No dependency signature reported
  • Long-term safety in Western populations not characterised

The Russian Semax label is the primary source; grey-market use inherits none of that framework.

  • Pregnancy and breastfeeding — inadequate data
  • Acute psychosis or unstable psychiatric conditions warrant caution
  • Not FDA / EMA / MHRA approved
  • Grey-market provenance is not equivalent to Russian Semax

Monitoring

  • Nasal mucosa tolerability
  • Cognitive / neurological symptom response
  • Any new or worsening psychiatric symptoms
Frequently asked questions
  • Is Semax an approved medicine?

    Yes — in Russia and some CIS countries, since 1994. It is dispensed by prescription as intranasal solutions in two strengths: Semax 0.1% for chronic use and Semax 1% for acute stroke. It has no MHRA / EMA / FDA authorisation.

  • How is Semax related to ACTH?

    Semax reproduces the ACTH(4-10) fragment — the portion of adrenocorticotropic hormone that carries neuromodulatory activity in the brain — with a Pro-Gly-Pro C-terminal extension that increases plasma stability and central nervous system penetration. The design keeps the brain-active fragment and drops the peripheral corticotropic (adrenal-stimulating) portion of the full hormone. Semax does not increase cortisol or engage the HPA axis in the way full-length ACTH does.

  • How does Semax differ from Selank?

    Both are Russian regulator peptides developed at the Institute of Molecular Genetics using the same Pro-Gly-Pro C-terminal extension strategy. Semax is an ACTH(4-10) analogue registered primarily for stroke, encephalopathy and cognitive indications. Selank is a tuftsin analogue registered primarily as an anxiolytic. Their approved indication sets are different because their parent sequences engage different neurological pathways.

  • Does Semax work for acute stroke?

    The Russian approved use of Semax 1% intranasal in acute ischaemic stroke is supported by the Gusev/Skvortsova Moscow clinical programme. Whether that evidence would translate into a Western approval under ICH-GCP standards is an untested question — no Western sponsor has run a large placebo-controlled trial in the acute-stroke window. In current Western practice, thrombolysis and mechanical thrombectomy are the standard-of-care acute-stroke interventions; Semax is not part of Western stroke guidelines.

  • Why isn't Semax available in the US or EU?

    The Russian regulatory registration is based on Russian clinical evidence; no Western sponsor has run ICH-GCP randomised placebo-controlled trials or submitted a regulatory dossier to the MHRA, EMA or FDA. Whether the compound could be authorised in Western markets given the current evidence is an open question that has not been formally tested.

References
  1. [1]

    Semax 1% intranasal solution in acute ischaemic stroke — Moscow clinical program supporting the Russian registrationGusev EI, Skvortsova VI, Miasoedov NF, et al., Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova (2005)

  2. [2]

    Extension of the Semax stroke clinical evidence base into the 2010s — Skvortsova continuation studiesSkvortsova VI, Gusev EI, et al., Russian neurological journals (2013)

  3. [3]

    Regulatory peptides Selank and Semax — a developer's consolidating review of design principles, chemistry and clinical evidenceMyasoedov NF, Russian Journal of Bioorganic Chemistry / review (2011)

  4. [4]

    Semax pharmaceutical registration documentation — Russian State Registry of Medicinal ProductsRussian State Registry of Medicinal Products, Regulatory registry documentation (1994)

  5. [5]

    Peptides & Compounds — The No-Jargon Guide (v5)Healthy Mango Editorial, Healthy Mango practitioner reference (2026)

Laboratory Reference Notice

This section summarizes procedures and study parameters reported in published scientific literature and laboratory protocols. It is provided for educational and research reference only and must not be interpreted as medical advice, clinical guidance, or instructions for personal use.

Editorial review pending

This page has not yet undergone external editorial review. Content is drawn from published sources and may be updated as review completes.

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