Semax research and evidence
Scope of this reference
This page describes the shape of the published research on Semax and the evidence tier of each finding. It is not a treatment guide, a recommendation, a human-use protocol or evidence that the listed material is safe or effective in people or animals. What the compound is and how it is classified is on the Semax identity page, and its nearest neighbour is compared on Semax and Selank.
The shape of the literature
This page maps selected Semax research by evidence tier; it is not a systematic review. For the Russian-language records, the summaries are limited to their English abstracts.
- Biochemistry and cell work. Two studies: binding and breakdown in rat brain membranes (Russia, 2004) and metal-binding chemistry with a neuroblastoma cell line (Italy, 2016).
- Rat studies. Six studies of learning tests, gene expression and induced brain injury, all in rats.
- Human studies. Two clinical series in patients, published in Russian in 1997 and 2005, and one placebo-controlled brain-imaging study in 52 healthy volunteers in 2020.
Nine of the eleven papers list the same author, N F Myasoedov, and where affiliations are given the rat work comes from Moscow institutes. The Italian chemistry paper and the 2005 clinical series do not list him. The rest read as one research programme, not as independent confirmations of each other.
In vitro and biochemical findings
- Binding and breakdown in rat brain membranes. Dolotov and colleagues (2004) reported specific, reversible, calcium-dependent binding of labelled Semax to plasma membranes from rat forebrain, with a dissociation constant of about 2.4 nM. Dipeptidyl aminopeptidases broke the peptide down stepwise, first to HFPGP and then to PGP, and its half-life in the presence of the membranes was longer than one hour. The abstract does not name the binding site.
- Copper and zinc chemistry. Magrì and colleagues (2016) showed that Semax and its N-acetyl form coordinate copper(II) and zinc(II) differently. In the SH-SY5Y neuroblastoma cell line, acetylating the amino terminus did not protect cells from copper toxicity, which the authors read as a role for the free amino group. This is coordination chemistry in one cell line, not a pharmacology claim.
These findings describe how the molecule behaves in a membrane preparation and in a test tube. They do not show what it does in an intact animal.
Rat findings
| Study | System | What was reported |
|---|---|---|
| Glazova and colleagues, 2005 | Rats, learning tests | Replacing the first residue (methionine) with glycine, threonine or alanine removed the learning effect. Lysine or a gluconic-acid modification kept it |
| Dolotov and colleagues, 2006 | Rat hippocampus after a single application | BDNF protein up about 1.4-fold, TrkB phosphorylation up 1.6-fold, exon III BDNF mRNA up 3-fold and TrkB mRNA up 2-fold, with more conditioned avoidance reactions |
| Agapova and colleagues, 2007 | Normal rat brain, one hour after treatment | Bdnf expression up in hippocampus, brainstem and cerebellum. Ngf up in hippocampus and down in frontal cortex |
| Dmitrieva and colleagues, 2009 | Rats after permanent middle cerebral artery occlusion | Semax raised transcription of several neurotrophin and receptor genes at 3, 24 and 72 hours. The Pro-Gly-Pro tripeptide alone overlapped only in part and was largely nonspecific |
| Stavchansky and colleagues, 2010 | Rats, incomplete global brain ischaemia (pilot study) | Semax and Pro-Gly-Pro increased proliferation of glial, endothelial and progenitor cells. Only Semax reduced ischaemic damage to the tissue |
| Glazova and colleagues, 2020 | Rats exposed to an antidepressant in early life | Semax given afterwards was reported to reduce anxiety-like behaviour and normalise brain monoamine levels in that model |
Three limits apply to every row. All of it is rat work, so none of it establishes anything about other species. Most findings are changes in messenger RNA or protein at one time point, which show association and not mechanism. And the work comes largely from one programme, with no independent replication among the records reviewed here.
Human data
Three human studies are cited here. Their designs differ, and none is a large randomised, double-blind trial.
- Acute stroke series, 1997. Gusev and colleagues compared 30 patients with acute hemispheric ischaemic stroke who received Semax alongside conventional care with 80 patients who received conventional care alone. PubMed classes it as a controlled clinical trial. The abstract does not describe randomisation, blinding or a placebo, and outcomes were clinical rating scales plus EEG and evoked-potential measures.
- Cerebrovascular insufficiency series, 2005. Gusev, Skvortsova and Chukanova examined 187 patients with cerebrovascular insufficiency and reported on tolerability and clinical course. PubMed classes it as an evaluation study. The abstract describes no placebo group or blinding.
- Healthy-volunteer imaging study, 2020. Panikratova and colleagues studied 52 healthy participants with resting-state functional MRI before and after Semax, Selank or placebo. They reported group differences in connectivity between the right amygdala and regions of the right temporal cortex. The outcome is a brain-imaging measure, and the abstract reports no cognitive or behavioural result.
The two clinical series concern people with cerebrovascular disease in a Russian clinical setting. This page does not reproduce the regimens described in those papers. The cited human records do not establish a large, blinded evidence base.
What cannot be concluded
- "Nootropic" as a demonstrated outcome. The word is a label used in the Russian literature and in retail copy. The learning findings are rat findings. None of the three human studies cited here reports a cognitive-performance result in healthy adults.
- A neurotrophin rise as a mechanism in people. The BDNF and NGF changes are measured in rat tissue at set times after treatment. None of the cited papers measures them in human brain.
- Findings in stroke patients as general claims. The clinical series concern a specific diagnosis in a specific health system, and they cannot be carried over to other populations or to a laboratory reagent.
- Equivalence with related molecules. The 2016 chemistry shows that N-acetyl Semax behaves differently from Semax, and the 2009 rat work found the Pro-Gly-Pro tripeptide alone did not match Semax. Evidence for one does not transfer to the other.
- Clinical use in Russia as UK authorisation. Use in clinical practice elsewhere, as the authors describe it, is not a UK or European licence.
Open questions
- Independent replication. Whether the neurotrophin findings hold in laboratories outside the original programme.
- Human tissue. Whether any of the reported changes can be measured in human brain.
- Controlled human trials. Randomised, blinded, placebo-controlled studies with pre-specified outcomes would be needed to move any claim above the clinical-series tier.
- The binding site. What the membrane binding reported in 2004 is attached to.
- Reagent versus studied material. Published work describes the material its authors used. Whether a given batch matches it is a question of identity and purity, which is what the COA publication status addresses.
EPS documentation
Use the research catalogue to check the exact name, labelled amount and format. The COA library publishes the original Janoshik reports selected for EPS, retaining the original report client name and any missing batch fields. Literature findings and another supplier's analytical results are not evidence about an EPS batch.
References
- Dolotov OV, Zolotarev IuA, Dorokhova EM, et al. The binding of Semax, ACTH 4-10 heptapeptide, to plasma membranes of the rat forebrain basal nuclei and its biodegradation (in Russian). Bioorg Khim. 2004;30(3):241-246.
- Dolotov OV, Karpenko EA, Inozemtseva LS, et al. Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. Brain Res. 2006;1117(1):54-60.
- Agapova TY, Agniullin YV, Shadrina MI, et al. Neurotrophin gene expression in rat brain under the action of Semax, an analogue of ACTH 4-10. Neurosci Lett. 2007;417(2):201-205.
- Dmitrieva VG, Povarova OV, Skvortsova VI, et al. Semax and Pro-Gly-Pro activate the transcription of neurotrophins and their receptor genes after cerebral ischemia. Cell Mol Neurobiol. 2009;30(1):71-79.
- Stavchansky VV, Yuzhakov VV, Botsina AYu, et al. The effect of Semax and its C-end peptide PGP on the morphology and proliferative activity of rat brain cells during experimental ischemia: a pilot study. J Mol Neurosci. 2010;45(2):177-185.
- Magrì A, Tabbì G, Giuffrida A, et al. Influence of the N-terminus acetylation of Semax, a synthetic analog of ACTH(4-10), on copper(II) and zinc(II) coordination and biological properties. J Inorg Biochem. 2016;164:59-69.
- Glazova NY, Manchenko DM, Volodina MA, et al. Semax, synthetic ACTH(4-10) analogue, attenuates behavioural and neurochemical alterations following early-life fluvoxamine exposure in white rats. Neuropeptides. 2020;86:102114.
- Panikratova YR, Lebedeva IS, Sokolov OY, et al. Functional connectomic approach to studying Selank and Semax effects. Dokl Biol Sci. 2020;490(1):9-11.
