Semax
An ACTH(4-7) fragment stripped of hormonal activity and stabilised with Pro-Gly-Pro.
Neuro & cognition · 7 min read · updated 13 Aug 2026
Research use only. The ranges below are what published studies and community protocols report. They are reference material for laboratory research, not medical advice or a recommendation for human or veterinary use.
The compound
Semax
View- Type
- Synthetic Peptide (ACTH Fragment Analog)
- CAS
- 80714-61-0
- Formula
- C₃₇H₄₉N₉O₁₀S
- Mass
- ~811.9 Da
At a glance
- Class
- Synthetic ACTH fragment analogue
- Sequence
- Met-Glu-His-Phe-Pro-Gly-Pro — 7 amino acids
- Molecular weight
- ~813.9 Da
- CAS
- 80714-61-0
- Primary route studied
- Intranasal
- Regulatory status
- Registered in Russia; not approved elsewhere
- Vial size stocked
- 10 mg
Semax is built from ACTH residues 4–7 with a Pro-Gly-Pro tripeptide attached to the C-terminus. Both halves of that design matter. The ACTH(4-7) fragment carries the neurotropic activity of adrenocorticotropic hormone without the corticotropic activity — it does not stimulate the adrenal cortex, because the region responsible for that sits elsewhere in the parent hormone. The Pro-Gly-Pro tail is a stabiliser: it slows enzymatic degradation enough to give the fragment a usable duration, and it is a naturally occurring motif in the endogenous regulatory-peptide system.
It was developed at the Institute of Molecular Genetics in Moscow and is a registered medicine in Russia, where it is used in ischaemic stroke and in cognitive and optic-nerve indications. Almost the entire clinical literature is Russian-language, which is the main reason it is unfamiliar in Western practice despite decades of use.
The mechanism most consistently reported is neurotrophic. Semax rapidly increases BDNF and NGF expression in the hippocampus and cortex — within hours of administration in rodent work — and the downstream effects on synaptic plasticity follow from that rather than from direct receptor agonism.
Mechanism in detail
- BDNF and NGF: rapid upregulation of both neurotrophin transcripts and their receptors TrkA and TrkB. This is the core finding and is reproduced across several independent rodent studies.
- Enkephalin protection: Semax inhibits enkephalin-degrading enzymes, prolonging endogenous opioid peptide signalling. This contributes to the analgesic and mood-related effects reported in the Russian literature.
- Monoamine modulation: effects on dopaminergic and serotonergic transmission are described, though less crisply than the neurotrophic work.
- Neuroprotection under ischaemia: reduced infarct volume and improved functional recovery in rodent middle cerebral artery occlusion models, which is the basis for the stroke indication.
- No corticotropic activity: repeatedly confirmed. Semax does not raise cortisol, which is the point of using the fragment rather than ACTH.
Why intranasal is the standard route
Semax is a hydrophilic seven-residue peptide and does not cross the blood–brain barrier efficiently from systemic circulation. The intranasal route exploits olfactory and trigeminal nerve pathways that deliver peptide to the central nervous system while largely bypassing the barrier — a route with real anatomical support rather than a convenience.
This is why Russian clinical formulations are nasal drops at 0.1% and 1%, and why intranasal dosing dominates reported protocols. Subcutaneous administration is used in some research contexts, but it is answering a different question about systemic exposure.
Formulating nasal drops from a vial
A vial holds at most 3 ml, so the dilute clinical concentrations are made in a separate sterile dropper bottle rather than in the vial: 10 mg reconstituted into 2 ml gives 0.5%, and 1 ml of that added to 4 ml of bacteriostatic water in the bottle gives 0.1% — the lower Russian clinical concentration. Reconstituted into 1 ml, the vial itself holds 1%. A standard nasal dropper delivers roughly 50 µl per drop, so a 0.1% solution provides about 0.05 mg per drop and a 1% solution about 0.5 mg per drop.
Sterility discipline matters more for nasal formulations than for injectables, because the container is repeatedly opened and the applicator repeatedly contacts mucosa. Bacteriostatic water, not plain sterile water, is the correct diluent.
Storage
- Lyophilised: 2–8 °C, or −20 °C for extended storage.
- Reconstituted: 2–8 °C, used within about 28 days for injectable preparations and rather less for a repeatedly opened nasal dropper.
- Protect from light; keep nasal bottles closed between uses.
Cautions
- The clinical evidence base is almost entirely Russian-language and has not been replicated in Western trials. That is a real limitation on how confidently any of it can be interpreted.
- Nasal irritation is the most commonly reported effect of the intranasal route.
- The absence of corticotropic activity is well established, but Semax is still an ACTH-derived peptide and has not been characterised for long-term continuous use.
- Interactions with monoamine-active compounds have not been studied.
References & credit
- 1Ashmarin IP et al., Zh Vyssh Nerv Deiat Im I P Pavlova 1997 — Original characterisation of Semax as a neurotropic ACTH(4-10) analogue family member.
- 2Dolotov OV et al., Brain Research 2006 — Semax and BDNF expression in rat hippocampus.
- 3Gusev EI, Skvortsova VI et al. — Russian clinical work on Semax in acute ischaemic stroke — the source of the high-dose protocol.
This article was written in-house. Where a dose range reflects community practice rather than a published trial, the community references we consulted are credited above and the article says which is which.