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.
Semax is a synthetic ACTH(4-10)-derived heptapeptide studied intranasally for BDNF-mediated cognition and post-stroke recovery; UK research-chemical status.
Evidence tier: A — ≥1 RCT + meta-analysis or approved clinical use
- 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, with a magnitude several-fold greater than baseline expression and persistence exceeding 24 hours after a single dose.
- 2Modulation of the endogenous opioid system through inhibition of enkephalin-degrading enzymes (neutral endopeptidase / neprilysin), transiently elevating brain enkephalin tone and contributing to the reported anxiolytic and mood-balancing effects.
- 3Direct neurotrophic signalling via TrkB (BDNF-cognate) and TrkA (NGF-cognate) receptor pathways downstream of BDNF/NGF release, activating PI3K-Akt, MAPK/ERK, and PLCγ cascades that stabilise activity-dependent synapses.
- 4Antioxidant and anti-inflammatory effects in cerebral ischaemia models — measurable reductions in lipid peroxidation markers (MDA, 4-HNE), preserved endogenous antioxidant enzyme activity, and modulation of microglial activation state following experimental stroke.
- 5Influence on serotonergic and dopaminergic neurotransmission — measured increases in 5-HT and dopamine metabolite levels in the prefrontal cortex and striatum, hypothesised to underlie observed effects on attention, motivation, and mood.
- 6Enhancement of long-term potentiation (LTP) in hippocampal slice electrophysiology — the cellular substrate of memory formation — with the effect operating downstream of the BDNF induction.
- 7Modulation of the HPA axis — attenuation of stress-induced corticosterone elevations in animal stress models, providing a mechanistic root for the observed anti-asthenic clinical effects.
- 8Angiogenic and neurogenic effects in the peri-infarct zone in stroke-recovery models — increased vascularisation and BrdU-labelled neurogenesis, contributing to the recovery phenotype reported in clinical rehabilitation work.
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 — replicated across rodent models (Morris water maze, radial-arm maze, novel-object recognition) and preliminary human studies in stroke recovery cohorts.
- 2Improved attention span and reduced mental fatigue under sustained-load conditions — the flagship benefit for the operator-population and post-viral asthenic-syndrome clinical use in Russia.
- 3Neuroprotection against ischaemic and oxidative injury in cerebrovascular research — the strongest evidence tier for Semax and the indication for which it received Russian regulatory approval in 1994.
- 4Reduction of anxiety-like behaviour in animal stress models — attributed to the enkephalinase-inhibition arm of the mechanism, complementary to the BDNF-mediated cognitive effect.
- 5Faster post-stroke recovery of speech and motor function in Russian-language clinical trials — measurable NIHSS and Barthel Index improvements over standard-of-care rehabilitation.
- 6Increased BDNF expression — a biomarker linked to neuroplasticity, mood resilience, and protection against cognitive decline, providing a mechanistic biomarker link between administration and cognitive outcome.
- 7Anti-asthenic effect — measurable reduction in mental fatigue and improvement in subjective wellbeing in post-viral, post-traumatic, and stress-related asthenic syndromes.
- 8Neuroprotective effect in optic-nerve ischaemia models — Semax has an approved Russian indication in some optic-neuropathy protocols, extending the neuroprotective evidence base beyond cerebral tissue.
Section 5
Theoretical Dosing & Protocols
| Route | Dosage | Frequency | Duration |
|---|---|---|---|
| Intranasal (research) | Typically 250–1000 μg per session in published Russian and Western research | 1–2 times daily in most study protocols | Study durations range from 10 days for acute-effect research to 12 weeks for chronic protocols; the Russian clinical protocols use 10–14 day cycles |
Note: Standard research protocol divides total daily dose across both nostrils, alternating sides between doses to preserve olfactory-epithelium delivery efficiency across a multi-day course.
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 transient nasal irritation, congestion, or dryness following intranasal application — the most common tolerability finding, typically self-limiting within the first 2–3 doses.
- · Transient mild headache reported in a minority of subjects, more common with the first several doses and generally resolving within the first week of a course.
- · Mild transient changes in alertness or arousal in early-dose research — usually described as improved focus rather than sedation.
- · Occasional altered dream quality during the first week of a course, without accompanying sleep-quality disturbance.
- · Rare mild gastrointestinal upset in high-dose animal work, not commonly observed at human research doses.
Rare / theoretical
- · Hypersensitivity reactions to peptide components — theoretical concern based on the amino-acid nature of the molecule; documented rates are very low in the Russian clinical experience.
- · Long-term human safety data outside the Russian Federation is limited — the majority of the clinical evidence originates from Russian trials.
- · Potential for pharmacodynamic interaction with monoamine-modulating drugs (MAOIs, SSRIs) given Semax's effect on monoamine turnover — no documented clinical events but a prudent research-context consideration.
- · Theoretical interaction with opioid-antagonist medications (naltrexone, naloxone) via the enkephalinase-inhibition arm of the mechanism.
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
Foundational preclinical study demonstrating that a single intranasal dose of Semax produced a marked rise in BDNF and NGF mRNA in the rat hippocampus within 3 hours of administration, with peak protein expression at 24 hours and persistence for at least 24–48 hours after a single dose. Provided the molecular-mechanism scaffold for the subsequent clinical work on cognitive and stroke-recovery endpoints.
Semax in ischaemic stroke rehabilitation
Multicentre Russian trial in acute-to-subacute ischaemic stroke populations reporting accelerated recovery of neurological function (NIHSS improvement, Barthel Index recovery) in the Semax-treated arm versus standard-of-care rehabilitation controls, with the differential most pronounced at day 21 and preserved at 90-day follow-up. Semax was administered adjunctively rather than as monotherapy.
Read studyEffects of Semax on attention and learning under load
Healthy adult subjects in an operator-simulation paradigm showed improved sustained-attention metrics (reaction time consistency, error rate under cognitive load) following a 10-day intranasal Semax protocol versus placebo, with the differential emerging by day 4 and consolidating over the second week of dosing.
Read studySemax in post-viral asthenic syndrome
Russian clinical experience in post-viral asthenic-syndrome cohorts reporting improvements in standardised asthenia inventories and subjective wellbeing scores over a 14-day intranasal Semax course, with an emerging clinical role in post-infectious cognitive-recovery contexts.
Semax mechanism of enkephalinase inhibition
Mechanistic biochemistry study demonstrating that Semax and its metabolites competitively inhibit brain enkephalin-degrading enzymes (neutral endopeptidase / neprilysin) at pharmacologically relevant concentrations, providing the molecular scaffold for the anxiolytic component of the peptide's clinical profile that operates alongside the BDNF-induction cognitive arm.
Section 10
Frequently Asked Questions
Section 10a
Practical Research Guidance
Cycle guidance
Reconstitution & storage
UK sourcing notes
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.