Semax at a glance
Semax is a synthetic heptapeptide, Met-Glu-His-Phe-Pro-Gly-Pro. Its opening four residues reproduce positions 4 to 7 of adrenocorticotropic hormone (ACTH), the pituitary signal that makes the adrenal glands secrete cortisol. The closing Pro-Gly-Pro triplet is foreign to ACTH and was attached because peptidases clear short, unprotected fragments almost at once. The literature classes the result as an ACTH(4-10) analogue with no corticotropic action: the behavioural properties of the fragment are kept, the cortisol drive is not.
The compound comes from the Institute of Molecular Genetics in Moscow, part of the Russian Academy of Sciences, and was formulated as nasal drops. Part of its pedigree is Dutch. In the 1960s the pharmacologist David de Wied found that ACTH fragments without any adrenal effect still changed avoidance learning in rats, proof that the endocrine and behavioural sides of the sequence can be pulled apart. The sister compound of Semax is Selank.
- Seven amino acids, 813.9 Da, with one methionine that oxidises easily.
- Registered in Russia as intranasal drops; no marketing authorisation in the EU.
- Main laboratory finding: more BDNF and more TrkB activity in the rat hippocampus.
- Human data: small Russian studies, the key one without a placebo arm.
How Semax works
No receptor for Semax has been firmly identified. Full-length ACTH reaches the adrenal gland through a melanocortin receptor, the family described in the Melanotan-2 profile, but that settles nothing about where this shortened fragment binds.
What has been measured lies downstream, in the neurotrophins. In rats, Semax increases brain-derived neurotrophic factor (BDNF) in the hippocampus, a structure needed for learning and memory, and it activates TrkB, the receptor through which BDNF signals. Further rat work from the Moscow institute found that vascular gene expression shifted after experimentally induced stroke, VEGF-family genes among them. The fact-checked material behind this profile contains no verified half-life, so none is quoted. How any of this relates to an effect in a patient is still a hypothesis.
The evidence ladder for Semax
| Evidence level | Model or trial | Main finding |
|---|---|---|
| Cell culture | Cultured rat glial cells, Moscow group, 2001 | Neurotrophin messenger RNA rose rapidly once Semax was in the medium |
| Animal study | Rats; Dolotov et al., Brain Research, 2006 | After one 50 µg/kg application, hippocampal TrkB phosphorylation rose 1.6-fold and BDNF protein by up to 1.4-fold; one BDNF transcript tripled and TrkB messenger RNA doubled |
| Small human study | Ischaemic stroke; Russian neurology journal, 1997 | 30 patients on Semax plus intensive care regained neurological function, motor function above all, faster than 80 on conventional care alone; no placebo group, no randomisation described |
| Licensed use | Russia only | Registered as intranasal drops; no authorisation from the EMA or the US FDA |
The ladder has solid lower rungs and then a gap. Cell and rat results agree with each other, yet they come largely from a single institute. The same is true of Epithalon, where nearly all data trace back to one research school.
On the clinical side, the 1997 report compared two groups of unequal size that were never shown to be alike at the start, so the faster recovery cannot be pinned on the peptide. Later Russian work on cognitive disorders is just as small and appears mainly in Russian. No large multinational randomised trial has been published. The ladder stops at small open comparisons.
Semax doses reported in studies
The values below are reference points from published work. They are not guidance, and none is an instruction for use in people.
| Setting | Dose | Schedule | Note |
|---|---|---|---|
| Rat hippocampus study (Dolotov et al., 2006) | 50 µg/kg | Single application | Scaled to body weight; not convertible to a human amount |
| Moderate ischaemic stroke (Russian report, 1997) | 12 mg a day | 5 days | Russian nasal product, added to standard care |
| Severe ischaemic stroke (same report) | 18 mg a day | 10 days | Russian nasal product, added to standard care |
| European Union | No authorised dose | – | Research material only |
The stroke rows show how a Russian nasal medicine was given in stroke units. No European regulator has reviewed that schedule.
Safety findings and open questions
Russian clinical reports call Semax well tolerated. They were small and short, so they could not detect uncommon events and say nothing about repeated courses over years. One risk that runs in the family seems to be absent: according to the reports, cortisol release is not triggered, in contrast to the parent hormone. Research-grade powder is not the Russian medicine, and no European body has evaluated it as one.
- What does repeated stimulation of BDNF and TrkB signalling do in healthy tissue over long periods? This has not been studied.
- How does Semax combine with other centrally acting drugs? Interactions are poorly characterised.
- How often do rare adverse events occur? The published studies are too small to tell.
- Does the neurotrophin response seen in the rat hippocampus occur in people at all?
Bench notes: storing and reconstituting Semax
Semax is supplied as a lyophilised powder, and the data panel gives −20 °C as its storage temperature. Keep the vial sealed, dry and out of the light, and let it warm to room temperature before opening so that no moisture condenses on the powder.
Methionine is the weak point of this sequence: it oxidises more readily than most residues, so limit the time a vial stands open. For reconstitution, laboratories normally use bacteriostatic water. Run the solvent slowly down the glass wall, swirl gently and do not shake. Keep solutions refrigerated and work from aliquots to avoid repeated freezing and thawing. Temperatures and shelf life for solutions are set out in the storage and reconstitution protocol.
Status in the Netherlands, Belgium and Luxembourg
EU marketing authorisations are issued through the European Medicines Agency and count in the Netherlands, Belgium and Luxembourg alike. Semax has none. Its only registration is Russian, as intranasal drops, and the sources for this profile know of no national authorisation in any member state.
In the Benelux, Semax is therefore a research chemical and not a medicine. Offering it to treat a condition would turn it into a medicinal product, and EU law demands an authorisation before that. National law on possession and personal import is not the same in every member state, and institutions add rules of their own, so check what applies to your laboratory. The primer on research peptides explains where the line between a medicine and research material runs.
The WADA Prohibited List does not mention Semax by name. Its S0 section, though, sweeps in any pharmacological substance that lacks approval for therapeutic use in humans, and how that treats a product registered in Russia and nowhere else is unsettled. Athletes in tested sport should ask their national anti-doping organisation.
Ordering Semax for research in the Benelux
King Peptides lists Semax 5 mg as a lyophilised research powder. Open the certificate of analysis for the current lot and check three things: HPLC purity is 99% or higher, the mass spectrum fits 813.9 Da, and the lot number equals the one on your vial. Oxidised methionine appears as a peak 16 Da above the expected mass, and a purity headline alone will not reveal it. Every lot has its own certificate with HPLC and mass spectrometry; the guide to checking a certificate of analysis goes through such a document line by line.
Orders are dispatched from the Netherlands in a tracked parcel. Delivery usually takes 1–2 business days within the Netherlands and 3–5 business days to Belgium and Luxembourg. Nothing crosses an external EU border, so there is no customs clearance. The wider supplier checklist is in the guide to buying research peptides in the Benelux.
Semax: quick answers
Does Semax raise cortisol? It is not reported to. The ACTH fragment it is built on lacks corticotropic activity, so the adrenal response to full-length ACTH is absent.
Which receptor does Semax act on? None has been firmly identified. The measured changes in BDNF and TrkB describe a consequence, not a binding site.
How strong is the stroke evidence? Weak by current standards. The 1997 Russian report set 30 treated patients against 80 on conventional care, with no placebo and no described randomisation.
Can Semax be obtained as a medicine in the Benelux? No. It has no EU marketing authorisation, so what is sold here is research material for laboratory use.
Research use only. This page describes Semax for laboratory and scientific research. Research material has no marketing authorisation, whatever the status of the molecule as a medicine elsewhere, and is not meant for human or veterinary use. Nothing on this page is medical advice; the doses above are those reported in published studies, not recommendations. Check the rules that apply in your country and at your institution before ordering.