Semax: ACTH(4-10) Analogue
A nootropic neuropeptide derived from ACTH fragment, extensively studied for cognitive enhancement and neuroprotection.
Quick Reference
| Research Dosage | 200-600mcg per day |
|---|---|
| Frequency | 1-2 times daily |
| Administration | Intranasal (common), subcutaneous |
| Cycle Length | 10-20 days typical, with breaks between cycles |
| Reconstitution | 2mL bacteriostatic water |
| Storage | Refrigerate, protect from air (methionine oxidation), use within 3-4 weeks |
Semax stands apart from typical research peptides – it's an approved pharmaceutical medication in Russia, prescribed since the early 1990s for stroke treatment, cognitive dysfunction, peptic ulcers, and optic nerve disease. This regulatory status means Semax has more clinical documentation, established dosing protocols, and safety data than virtually any other nootropic peptide.
Derived from adrenocorticotropic hormone (ACTH), Semax was specifically engineered to retain the cognitive-enhancing properties of ACTH while eliminating its hormonal effects on cortisol and the adrenal system. The result is a compound that enhances brain function through neurotrophin modulation – particularly BDNF (brain-derived neurotrophic factor) – without affecting the stress hormone axis.
What makes Semax particularly interesting for neuroscience research is its documented ability to cross the blood-brain barrier and produce measurable changes in gene expression affecting hundreds of genes related to neuroplasticity, neuroprotection, and immune function.
Research Applications
Semax is studied across multiple domains of neuroscience and cognitive research:
Cognitive Enhancement Research
BDNF and Neurotrophin Expression
Semax's most documented mechanism involves brain-derived neurotrophic factor:
- Research demonstrates significant upregulation of BDNF expression in hippocampus and cortex
- BDNF is critical for neuronal survival, synaptic plasticity, and memory formation
- Effects on NGF (nerve growth factor) and other neurotrophins also documented
- Enhanced neurotrophin signalling may underlie cognitive effects
Memory and Learning Studies
Russian clinical research has examined Semax's effects on:
- Short-term and long-term memory consolidation
- Learning acquisition and retention
- Information processing speed
- Working memory capacity
- Attention and concentration
Cognitive Protection Under Stress
Studies have investigated whether Semax protects cognitive function under adverse conditions:
- Hypoxia (low oxygen) models
- Chronic stress paradigms
- Sleep deprivation effects
- Age-related cognitive decline
- Neurotoxic challenge models
Neuroprotection Research
Stroke and Ischemia (Russian Approved Indication)
In Russia, Semax is approved for stroke treatment. Research has examined:
- Acute ischemic stroke outcomes
- Reduction of infarct volume
- Post-stroke cognitive recovery
- Protection against ischemia-reperfusion injury
- Neuronal survival in oxygen-deprived conditions
- Functional recovery following cerebrovascular events
Mechanisms of Neuroprotection
Studies suggest Semax protects neurons through multiple pathways:
- Antioxidant enzyme upregulation
- Reduced apoptosis (programmed cell death)
- Mitochondrial function preservation
- Anti-inflammatory effects in neural tissue
- Neurotrophic support maintaining cell viability
Dopamine System Research
Studies show Semax significantly affects dopamine pathways:
- Modulates dopamine metabolism and turnover
- Affects dopamine receptor expression (D1 and D2 subtypes)
- Influences tyrosine hydroxylase (rate-limiting enzyme in dopamine synthesis)
- May affect dopamine transporter function
Given dopamine system effects, research has explored applications in attention deficit models, Parkinson's disease models (dopaminergic neuroprotection), reward and motivation research, and cognitive symptoms of dopamine dysfunction.
Optic Nerve and Vision Research
Semax has been studied for optic nerve conditions in Russia:
- Optic nerve atrophy
- Glaucoma-related optic neuropathy
- Visual pathway dysfunction
- Retinal ganglion cell protection
Immune Modulation Research
Research documents broad effects on immune-related genes:
- Alters expression of genes modulating immune cell activity
- Enhances chemokine and immunoglobulin gene expression
- Affects cytokine profiles
- May influence neuroimmune interactions
Dosage Information
Standard Research Dosages
Dosages commonly referenced in Russian clinical literature and research protocols range from 200-600mcg per day, typically divided into 1-2 administrations.
Dosing Protocols
Conservative: 200-300mcg once daily
Standard: 300mcg twice daily (600mcg total)
Higher range: Up to 900mcg daily in some research protocols
Administration Routes
Intranasal Administration
- Most common route in Russian clinical use
- Formulated as 0.1% and 1% nasal spray solutions
- Rapid absorption through nasal mucosa
- Direct access to CNS via olfactory pathway
Subcutaneous Injection
- Alternative research route
- Systemic absorption
- May have different pharmacokinetic profile than intranasal
Cycle Duration and Structure
Research protocols typically employ cycling:
- Active period: 10-20 days
- Break period: Equal duration or longer
- Rationale: Allows assessment of sustained effects, prevents potential tolerance
Timing Considerations
- Morning administration aligns with natural cognitive demands
- Some protocols use morning + early afternoon dosing
- Evening dosing less common due to potential alertness effects
Reconstitution Guide
Required Materials
- Semax lyophilised powder
- Bacteriostatic water
- Sterile syringe
- Alcohol swabs
Reconstitution Steps
- Allow vial to reach room temperature
- Draw 2mL bacteriostatic water into syringe
- Add water slowly, directing stream down inside vial wall – do not spray onto powder
- Allow to dissolve without shaking. Semax typically dissolves readily.
- Minimise air exposure during reconstitution (methionine oxidation concern)
- Store immediately refrigerated at 2-8°C
Concentration Reference Table
| Vial Size | Water Added | Concentration | 300mcg Dose | 600mcg Dose |
|---|---|---|---|---|
| 10mg | 2mL | 5mg/mL | 6 units (0.06mL) | 12 units (0.12mL) |
| 30mg | 3mL | 10mg/mL | 3 units (0.03mL) | 6 units (0.06mL) |
Storage Guidelines
Critical Note: Methionine Oxidation
Semax contains an N-terminal methionine residue that is susceptible to oxidation. Oxidised Semax may have altered biological activity.
Protection Measures
- Minimise air exposure when drawing doses
- Keep vial sealed when not in use
- Store in dark location (light can accelerate oxidation)
- Use within recommended timeframe
Lyophilised (Powder) Form
- Long-term: -20°C (freezer)
- Short-term: 2-8°C (refrigerator) for up to several weeks
- Protect from light and moisture
Reconstituted Solution
- Must be refrigerated at 2-8°C
- Use within 3-4 weeks
- Minimise air in vial
- Discard if discoloration occurs
Semax vs Selank: Understanding the Difference
Both Semax and Selank are Russian-developed heptapeptide nootropics, often discussed together but with distinct profiles:
| Property | Semax | Selank |
|---|---|---|
| Derived From | ACTH(4-10) | Tuftsin |
| Amino Acids | 7 | 7 |
| Primary Research Focus | Cognition, neuroprotection | Anxiety, mood stabilisation |
| BDNF Effects | Strong upregulation | Moderate upregulation |
| Anxiolytic Effects | Mild/secondary | Strong/primary |
| Dopamine Effects | Significant | Moderate |
| GABA Effects | Minimal | Significant |
| Immune Effects | Moderate | Strong (tuftsin component) |
| Russian Approval | Stroke, cognitive disorders | Anxiety, neurasthenia |
Complementary Use
Some researchers study both peptides together based on complementary mechanisms:
- Semax for cognitive enhancement and neuroprotection
- Selank for anxiolytic effects and mood stabilisation
- Different receptor targets with potential synergy
- No documented negative interactions
Frequently Asked Questions
Common questions about Semax research
What is Semax?
Semax is a synthetic heptapeptide (7 amino acids) derived from ACTH(4-10), the cognitive-active fragment of adrenocorticotropic hormone. Developed in Russia, it's approved there as a pharmaceutical for stroke treatment and cognitive disorders. Research focuses on its nootropic (cognitive-enhancing) and neuroprotective properties, primarily mediated through BDNF upregulation.
Is Semax approved anywhere?
Yes. Semax is approved as a pharmaceutical medication in Russia for several indications including ischemic stroke, cognitive disorders, and optic nerve conditions. It has been prescribed clinically since the early 1990s. It is not approved by the FDA, TGA, or European regulatory agencies.
What does Semax do to the brain?
Research shows Semax significantly increases BDNF and other neurotrophin expression, modulates dopamine and serotonin neurotransmitter systems, provides neuroprotective effects against ischemia and oxidative stress, affects expression of hundreds of genes related to neuroplasticity, and enhances cognitive functions including memory and attention in research models.
How is Semax different from Selank?
Semax is derived from ACTH and primarily targets cognition and neuroprotection through BDNF upregulation and dopamine modulation. Selank is derived from tuftsin (an immune peptide) and primarily targets anxiety and mood through GABA system modulation. Semax is more "stimulating/cognitive" while Selank is more "calming/anxiolytic."
Does Semax affect cortisol like ACTH?
No. Full ACTH stimulates the adrenal glands to release cortisol. Semax uses only the ACTH(4-10) fragment, which retains cognitive effects while lacking the hormonal sequence that stimulates cortisol release. Research confirms Semax does not significantly affect cortisol or the HPA axis at standard doses.
How is Semax typically administered?
In Russian clinical use, Semax is administered intranasally as a 0.1% or 1% solution (nasal spray/drops). Research applications may also use subcutaneous injection. Intranasal administration provides rapid absorption and potential direct CNS access via olfactory pathways.
What is the onset of effects with Semax?
Acute cognitive effects may be noticeable within hours of administration. Changes in neurotrophin expression and gene regulation develop over days of consistent use. Full effects on cognitive performance typically assessed over 10-20 day treatment periods.
How should Semax be stored?
The N-terminal methionine in Semax is susceptible to oxidation. Store lyophilised powder frozen (-20°C) or refrigerated. After reconstitution, refrigerate and use within 3-4 weeks. Minimise air exposure and protect from light.
What is the molecular weight of Semax?
Semax has a molecular weight of 813.97 g/mol (Da).
Can Semax and Selank be used together?
Research has examined both peptides without reported negative interactions. They have complementary mechanisms – Semax for cognition/neuroprotection, Selank for anxiety/mood. Some protocols use both concurrently.
The Science: How Semax Works
Origin: The ACTH Fragment
Semax was designed based on ACTH(4-10), a fragment of adrenocorticotropic hormone:
Full ACTH (39 amino acids)
- Released by pituitary in response to stress
- Stimulates adrenal cortex to produce cortisol
- Has documented cognitive/neurotrophic effects as secondary property
ACTH(4-10) Fragment (7 amino acids)
- Retains the cognitive-enhancing effects of ACTH
- Lacks the sequence (positions 1-3 and beyond 10) required for adrenal stimulation
- No significant cortisol or HPA axis effects
Semax Modification
- Pro-Gly-Pro tripeptide added to C-terminus
- Increases stability against enzymatic degradation
- Extends biological half-life
- Improves brain penetration
Mechanism of Action
1. Neurotrophin Expression (Primary Mechanism)
Semax significantly upregulates neurotrophins, particularly BDNF:
- BDNF (Brain-Derived Neurotrophic Factor): Critical for neuronal survival, synaptic plasticity, and neurogenesis. Semax increases BDNF mRNA and protein in hippocampus and cortex.
- NGF (Nerve Growth Factor): Neuronal support and survival
- CNTF (Ciliary Neurotrophic Factor): Neuronal protection
- NT-3, NT-4: Additional neurotrophic support
2. Dopamine System Modulation
Research shows significant effects on dopaminergic neurotransmission:
- Modulates dopamine turnover and metabolism
- Affects expression of D1 and D2 dopamine receptors
- Influences tyrosine hydroxylase expression (dopamine synthesis)
- May affect dopamine transporter (DAT) function
3. Gene Expression Profile
Microarray and RNA sequencing studies reveal broad genomic effects:
Genes Upregulated:
- Bdnf, Ngf, Ntf3 (neurotrophins)
- Bcl-2, Bcl-xL (anti-apoptotic)
- Antioxidant response genes
- Synaptic plasticity genes
Genes Downregulated:
- Pro-apoptotic genes
- Inflammatory mediators
- Stress response genes (in excess)
4. Neuroprotective Mechanisms
Multiple pathways contribute to neuroprotection:
- Antioxidant Effects: Upregulates antioxidant enzyme expression, reduces oxidative damage markers
- Anti-Apoptotic Effects: Increases Bcl-2 family survival proteins, reduces caspase activation
- Anti-Inflammatory Effects: Modulates microglial activation, reduces pro-inflammatory cytokines
5. Blood-Brain Barrier Penetration
Semax crosses the blood-brain barrier:
- Small peptide size facilitates transport
- Intranasal administration may provide direct CNS access
- Brain penetration confirmed by central effects and tissue studies
Amino Acid Sequence and Structure
Full Sequence (Three-Letter Code): Met-Glu-His-Phe-Pro-Gly-Pro
Single-Letter Code: MEHFPGP
Structural Features
- N-Terminal Methionine: Susceptible to oxidation (methionine sulfoxide formation), requires protection from air and light
- ACTH(4-7) Core: Met-Glu-His-Phe represents the active core essential for cognitive activity
- C-Terminal Pro-Gly-Pro Extension: Provides resistance to peptidases, extends biological half-life
Technical Specifications
| Systematic Name | Semax |
|---|---|
| Other Names | ACTH(4-10) Analogue, ACTH 4-10, Heptapeptide Semax, MEHFPGP, Semax Acetate, N-Acetyl Semax, Adamax |
| Amino Acid Count | 7 |
| Sequence | MEHFPGP |
| Molecular Formula | C37H51N9O10S |
| Molecular Weight | 813.97 g/mol |
| CAS Number | 80714-61-0 |
| Isoelectric Point | ~5.5 |
| Net Charge (pH 7) | Variable (pH dependent) |
| Appearance | White to off-white lyophilised powder |
| Solubility | Freely soluble in water and aqueous buffers |
| Purity (PurposeLabs) | ≥99% (HPLC verified) |
| Storage (Lyophilised) | -20°C long-term, 2-8°C short-term |
| Storage (Reconstituted) | 2-8°C, use within 4-6 weeks |
Quality: Australian University Testing
Why Peptide Quality Matters
The research peptide market contains products of highly variable quality. Independent testing of products from various suppliers has revealed significant issues:
- Purity levels as low as 50% in products claiming "99% purity"
- Incorrect amino acid sequences (entirely wrong peptides)
- Truncated sequences (missing amino acids)
- Bacterial endotoxin contamination
- Oxidised or degraded peptides with reduced activity
Our Testing Protocol
Every batch of Semax from PurposeLabs undergoes comprehensive testing at a leading proteomics laboratory based at an Australian university in Sydney – one of Australia's premier analytical facilities.
Confirms purity levels of ≥99%, identifies any impurities or degradation products.
Verifies exact molecular weight, confirms correct amino acid sequence.
Determines actual peptide content versus salt, moisture, and counter-ions.
Why Australian University Testing?
Our testing partner is an established, verifiable proteomics facility at a major Australian university, with published research credentials, transparent methodology, and no commercial conflict of interest. This contrasts with overseas "certificates of analysis" from unknown or unverifiable laboratories.
Shop Semax
Australian university tested. 99%+ purity verified by HPLC and mass spectrometry. Fast shipping from Sydney.
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References
Key studies for researchers seeking primary literature:
- Eremin KO, et al. "Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents." Neurochemical Research, 2005.
- Dolotov OV, et al. "Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus." Brain Research, 2006.
- Gusev EI, Skvortsova VI. "Brain ischemia." Kluwer Academic/Plenum Publishers, 2003. (Includes Semax clinical data from Russian stroke trials)
- Kolomin T, et al. "Transcriptomic response of rat hippocampus and spleen to single and repeated administration of Semax." Frontiers in Neuroscience, 2013.
- Agapova TY, et al. "Effect of Semax on the temporal dynamics of brain-derived neurotrophic factor and nerve growth factor gene expression in the rat hippocampus and frontal cortex." Neuroscience and Behavioral Physiology, 2008.
- Levitskaya NG, et al. "Nootropic and analgesic effects of Semax given different routes." Rossiiskii Fiziologicheskii Zhurnal, 2008.
- Shadrina M, et al. "Transcriptomic studies of the effect of neuroprotective peptide Semax on gene expression in human lymphocytes." Molecular Biology, 2010.
- Grivtsova LY, et al. "Semax in the treatment of optic nerve atrophy." Vestnik Oftalmologii, 2002.
Disclaimer
All products sold by PurposeLabs are intended for laboratory and research use only. They are not intended for human or animal consumption. The information provided is for educational purposes only and should not be construed as medical advice. Consult with qualified healthcare professionals for any health-related decisions.
Semax is not approved by the TGA for therapeutic use in Australia. Products are sold strictly for research purposes in accordance with Australian regulations.