Selank vs Semax
Selank and Semax are both synthetic heptapeptides developed at the Institute of Molecular Genetics in Moscow, and both carry a C-terminal Pro-Gly-Pro tripeptide that confers resistance to enzymatic degradation. Selank derives from the immunomodulatory tetrapeptide tuftsin and has been studied as an anxiolytic; Semax consists of the ACTH(4-7) fragment and is registered in Russia for ischaemic stroke, optic nerve disease and cognitive indications. Their common origin, shared structural motif and adjacent indications mean they are frequently discussed as a pair. Unlike most compound pairings in this library, direct comparative data exist: at least three published studies administered both peptides within a single design, including one placebo-controlled human neuroimaging study in 52 participants. Those studies characterise differing effects rather than ranking one above the other.
They have been compared directly.
Panikratova and colleagues scanned 52 healthy participants with resting-state fMRI before administration and again 5 and 20 minutes afterwards, with participants receiving Semax, Selank or placebo. Between-group and between-condition differences were found in functional connectivity between the right amygdala and a right-hemisphere region spanning fusiform, inferior and middle temporal and parahippocampal gyri, and post hoc analysis distinguished effects common to both peptides from effects specific to each. Kost and colleagues had earlier shown in human serum that both peptides inhibit enkephalin-degrading enzymes in a dose-dependent manner, reporting an IC50 of 10 microM for Semax and 20 microM for Selank, with both more potent in that assay than puromycin or bacitracin. Slominsky and colleagues gave both peptides to rats with 6-hydroxydopamine-induced parkinsonism and reported that neither altered motor activity or passive defensive behaviour, while Selank alone reduced anxiety measures in the elevated cross maze. These are small mechanistic and imaging studies with surrogate endpoints rather than comparative clinical trials, so they describe divergent signatures without establishing relative clinical usefulness.
The 3 studies that tested both
- 01Human clinical2020
Functional Connectomic Approach to Studying Selank and Semax Effects
Panikratova YR, et al. · Dokl Biol Sci · placebo-controlled resting-state fMRI in 52 healthy participants; Semax, Selank or placebo, with scanning before and at 5 and 20 minutes after injection; regions of interest were the left and right amygdala and dorsolateral prefrontal cortex
Between-group and between-condition differences were observed in functional connectivity between the right amygdala and a right-hemisphere region covering fusiform, inferior and middle temporal and parahippocampal gyri. Post hoc analysis identified both shared and compound-specific effects of Selank and Semax on that connection, which the authors described as a first report.
- 02Animal in vivo2017
Peptides semax and selank affect the behavior of rats with 6-OHDA induced PD-like parkinsonism
Slominsky PA, et al. · Dokl Biol Sci · rats with 6-hydroxydopamine-induced Parkinson-like lesions of the substantia nigra; both Semax and Selank administered, with elevated cross maze and passive defensive behaviour testing
Neither peptide affected motor activity in the elevated cross maze or passive defensive behaviour. Selank reduced anxiety measures in lesioned rats, an effect the authors noted had previously been reported in healthy rodents, and they concluded that toxic damage to the substantia nigra did not alter the response to Selank.
- 03In vitro2001· Russian (English abstract)
[Semax and selank inhibit the enkephalin-degrading enzymes from human serum]
Kost NV, et al. · Bioorg Khim · enzymology in human serum; dose-response testing of the synthetic heptapeptides Semax and Selank and of their tri-, tetra-, penta- and hexapeptide fragments against enkephalin-degrading enzymes
Both peptides inhibited enkephalin-degrading enzymes dose-dependently, with a reported IC50 of 10 microM for Semax and 20 microM for Selank, more pronounced than puromycin, bacitracin and several other peptidase inhibitors. The pentapeptide fragments were also inhibitory, while the tri-, tetra- and hexapeptide fragments were not.
Side by side.
| Selank | Semax | |
|---|---|---|
| Evidence maturity | Early clinical | Approved drug |
| Studies cited here | 15 | 18 |
| Published 2023 or later | 0 | 10 |
| Newest paper | 2022 | 2025 |
| Parent molecule | Thr-Lys-Pro-Arg-Pro-Gly-Pro, derived from the immunomodulatory tetrapeptide tuftsin with a C-terminal Pro-Gly-Pro extension. | Met-Glu-His-Phe-Pro-Gly-Pro, the ACTH(4-7) fragment with the same C-terminal Pro-Gly-Pro extension. It lacks corticotropic activity. |
| Proposed mechanism | Inhibition of enkephalin-degrading enzymes, modulation of GABA-A receptor signalling, and regulation of BDNF and inflammation-related gene expression, including shifts in Th1/Th2 cytokine balance. | Regulation of BDNF and NGF expression and broad transcriptomic modulation of inflammatory and neurosignalling genes, characterised mainly in rodent cerebral ischaemia models. Separate in vitro work describes copper chelation and interaction with amyloid beta. |
| Regulatory status | Not an approved medicine outside Russia and not registered under EMA or FDA review; studied clinically within Russia in anxiety indications. | Registered in Russia for ischaemic stroke, optic nerve disease and cognitive indications. No trial has been registered or completed under EMA or FDA standards. |
| Human evidence base | A small number of Russian comparative trials in generalised anxiety disorder, neurasthenia and phobic-anxiety and somatoform disorders, several using active comparators such as medazepam or phenazepam rather than placebo, plus one placebo-controlled fMRI study. | Russian clinical studies in acute and post-acute ischaemic stroke, optic nerve disease and motor neuron disease, largely open-label or actively controlled, plus two small placebo-controlled resting-state fMRI studies in healthy volunteers. |
| Best-studied endpoint | Anxiety rating scales, including Hamilton, Zung and CGI, alongside benzodiazepine-sparing outcomes and quality-of-life measures in combination-treatment designs. | Stroke recovery measures such as the Barthel index and plasma BDNF, plus transcriptomic profiles in the rat transient middle cerebral artery occlusion model. |
| Current research activity | No primary Selank research articles indexed in PubMed after 2022, and no Phase III programme exists. | Active preclinical output through 2025, including Alzheimer's disease and spinal cord injury models, calcium imaging in brain slices and post-stroke transcriptomics. |
| Evidence in healthy adults | Effects on cognition in healthy adults are unestablished; the only healthy-volunteer data are from the shared 52-participant fMRI study. | Supported only by two small fMRI studies with surrogate imaging endpoints, one being the shared 52-participant study and the other a 24-volunteer default mode network study. |
And what it does not.
This pair is unusual in having genuine head-to-head data, but the data answer a narrower question than the pairing implies. The 52-participant fMRI study established that both peptides altered right amygdala connectivity and that some of those effects were compound-specific, which is an imaging observation rather than a clinical outcome. The serum enzymology showed both inhibit enkephalin-degrading enzymes, with Semax roughly twice as potent in that particular assay, and the rat parkinsonism study found an anxiety effect for Selank that was not attributed to Semax. Beyond those three studies the literatures diverge into different indications entirely, and both share the same structural limitation: almost all of the work originates from a small group of Russian laboratories, independent Western replication is absent, no double-blind placebo-controlled programme has run under EMA or FDA standards, and no pharmacokinetic or long-term safety data exist in Western populations. Neither compound has evidence supporting cognitive enhancement in healthy adults.
Common questions.
- Has a single study given both peptides to the same group of people?
A 2020 placebo-controlled resting-state fMRI study did, in 52 healthy participants who received Semax, Selank or placebo, with scans before administration and at 5 and 20 minutes afterwards. It reported both shared and compound-specific effects on connectivity between the right amygdala and right temporal cortex. It measured imaging connectivity rather than symptoms or task performance, so it does not establish a clinical difference between the two.
- What does the shared Pro-Gly-Pro tail actually do?
It is the structural feature that confers resistance to enzymatic degradation, which is why both peptides survive long enough to act after administration. The 2001 human serum enzymology found that pentapeptide fragments of both heptapeptides retained inhibitory activity against enkephalin-degrading enzymes while tri-, tetra- and hexapeptide fragments did not, indicating that the tail is not the sole determinant of that activity.
- Which of the two has been tested against a placebo rather than another drug?
Both have placebo-controlled data only in small neuroimaging studies. The Russian clinical trials of Selank in anxiety disorders were largely comparative against medazepam or phenazepam, or tested phenazepam with and without Selank. The Russian Semax studies in stroke, optic nerve disease and motor neuron disease were largely open-label or compared against conventionally treated controls. Neither compound has a completed double-blind placebo-controlled clinical outcome trial.
- Did the rat Parkinson's model separate the two peptides?
Partly. In rats with 6-hydroxydopamine-induced nigral lesions, neither peptide changed motor activity in the elevated cross maze or passive defensive behaviour. Selank reduced anxiety measures in those animals, which the authors noted matched effects previously seen in healthy rodents, and they concluded that the nigral damage did not alter the response to Selank. No corresponding anxiety effect was attributed to Semax in that report.
- Why is Semax classed as an approved drug while Selank is not?
Semax holds Russian marketing authorisation for ischaemic stroke, optic nerve disease and cognitive indications, granted on the basis of domestic trials that were largely open-label or actively controlled rather than double-blind and placebo-controlled. Selank carries no equivalent registration in the sources reviewed here. Neither has been assessed under EMA or FDA review, so the difference in status reflects one national regulatory process rather than a difference in the strength of trial evidence.
For research purposes only. Not for human consumption, diagnosis, treatment, or prevention of any condition. Nothing on this page is medical advice, and no comparison here should be read as a recommendation of either compound.