Semax
Also known as: Met-Glu-His-Phe-Pro-Gly-Pro · ACTH(4-10) analogue
A synthetic heptapeptide analogue of ACTH(4-10) developed in Russia for cognitive enhancement, neuroprotection, and stroke recovery research.
- Category
- Cognitive Enhancement
- Half-life
- Intranasal: minutes (peptide); BDNF effects persist 24h+
- Formula
- C₃₇H₅₁N₉O₁₀S
- Weight
- 813.93 g/mol
- Sequence
- Met-Glu-His-Phe-Pro-Gly-Pro
Section 1
Overview
Semax is a synthetic seven-amino-acid peptide derived from the 4–10 fragment of adrenocorticotropic hormone (ACTH). The natural ACTH fragment was historically observed to influence learning and memory in animal studies; Semax was engineered to retain those neurotropic effects while stripping the corticotropic (cortisol-releasing) activity, producing a peptide with cognitive activity but no steroid-axis side effects.
The molecule was developed at the Institute of Molecular Genetics of the Russian Academy of Sciences in the 1980s and entered clinical use in Russia in the late 1990s. It is administered intranasally in human research because the small peptide crosses the nasal mucosa and reaches the central nervous system without significant systemic exposure.
In laboratory studies, Semax has been characterised as a potent upregulator of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) expression in the hippocampus and prefrontal cortex — the two neurotrophins most closely associated with neuroplasticity, learning, and memory consolidation.
Section 2
Discovery & History
- Originally synthesised in the 1980s by researchers at the Institute of Molecular Genetics of the Russian Academy of Sciences, with the explicit goal of producing a cognitive-acting ACTH derivative free of the hormone's endocrine effects.
- Granted clinical approval in the Russian Federation in 1994 for cerebrovascular indications, and added to the Russian List of Vital and Essential Drugs in subsequent revisions.
- Outside Russia, Semax has remained a research chemical. Western academic groups began publishing on its mechanism and BDNF-induction properties through the 2000s and 2010s, expanding the international peer-reviewed literature.
- A more stable analogue, N-Acetyl Semax Amidate, was later developed to extend the peptide's half-life and is widely studied alongside the parent compound.
Section 3
Mechanism of Action
- 1Upregulation of BDNF and NGF transcription in the hippocampus within hours of intranasal administration in rodent models — the central plank of its pro-cognitive action.
- 2Modulation of the endogenous opioid system: Semax has been shown to inhibit enkephalin-degrading enzymes, transiently elevating brain enkephalin tone and contributing to its reported anxiolytic and mood-balancing effects.
- 3Direct neurotrophic signalling via TrkB and TrkA receptor pathways, downstream of BDNF/NGF release.
- 4Antioxidant and anti-inflammatory effects in cerebral ischaemia models: reduces lipid peroxidation markers and modulates microglial activation following experimental stroke.
- 5Influence on serotonergic and dopaminergic neurotransmission, hypothesised to underlie observed effects on attention, motivation, and mood in early-phase clinical research.
Section 4
Researched Benefits
Findings reported in the published preclinical and clinical literature. Effects in research contexts do not constitute claims of therapeutic benefit in humans.
- 1Enhanced memory consolidation and recall in learning tasks (rodent models, preliminary human studies in stroke recovery cohorts).
- 2Improved attention span and reduced mental fatigue under sustained-load conditions.
- 3Neuroprotection against ischaemic and oxidative injury in cerebrovascular research.
- 4Reduction of anxiety-like behaviour in animal stress models, attributed to enkephalinase inhibition.
- 5Faster post-stroke recovery of speech and motor function in Russian-language clinical trials (rehabilitation context).
- 6Increased BDNF expression — a biomarker linked to neuroplasticity, mood resilience, and protection against cognitive decline.
Section 5
Theoretical Dosing & Protocols
| Route | Dosage | Frequency | Duration |
|---|---|---|---|
| Intranasal (research) | Typically 250–1000 μg per session in published research | 1–2 times daily in study protocols | Study durations range from 10 days to 12 weeks |
Note: Standard research protocol divides total daily dose across both nostrils.
Section 6
Administration Routes
- Intranasal — primary route in all human research; bypasses first-pass metabolism and reaches CNS via the olfactory and trigeminal pathways.
- Subcutaneous and intravenous — used in some animal research but rare in human studies due to rapid plasma proteolysis.
- Oral administration is not viable: the peptide is rapidly degraded by gastrointestinal proteases.
Section 7
Safety Profile
Commonly reported
- · Mild nasal irritation following intranasal application
- · Transient mild headache reported in a minority of subjects
- · Mild transient changes in alertness or arousal in early-dose research
Rare / theoretical
- · Hypersensitivity reactions to peptide components (theoretical)
- · Long-term human safety data outside the Russian Federation is limited
- · Potential for interaction with monoamine-modulating drugs has not been comprehensively studied
Contraindications
- · Not authorised for human use in the UK/EU/US
- · Pregnancy and lactation — no controlled human data
- · Acute psychiatric crises — research subjects are typically excluded from trials in these states
Section 8
UK & EU Regulatory Context
United Kingdom
Not licensed as a medicine in the United Kingdom. Sold strictly as a research chemical for in vitro and preclinical laboratory use.
European Union
Not approved by the European Medicines Agency. Licensed for clinical use in the Russian Federation; not authorised elsewhere in the EU.
Section 9
Clinical Studies Summary
Semax modulates BDNF/NGF expression in rat hippocampus
Single intranasal dose produced a marked rise in BDNF and NGF mRNA in the hippocampus within 3 hours, persisting for at least 24 hours.
Semax in ischaemic stroke rehabilitation
Multicentre Russian trial reporting accelerated recovery of neurological function in patients receiving adjunct Semax versus standard care.
Effects of Semax on attention and learning under load
Healthy adult subjects showed improved sustained-attention metrics following a 10-day intranasal protocol versus placebo.
Section 10
Frequently Asked Questions
Section 11
Sourcing for Laboratory Research
Sourcing Semax for laboratory research
Researchers in the United Kingdom and elsewhere typically obtain Semax from specialist research-chemical suppliers. Purity, third-party testing, and supplier transparency are the principal differentiators worth evaluating before placing an order. The two suppliers below are commonly referenced in UK research contexts.
Reminder: research peptides are sold strictly for in vitro and preclinical laboratory purposes. Importation or supply for human consumption is not permitted under UK medicines legislation.