What are Semax and Selank
Semax is the heptapeptide Met-Glu-His-Phe-Pro-Gly-Pro. The first four residues correspond to the fragment ACTH 4-7 from adrenocorticotropic hormone. The C-terminal Pro-Gly-Pro sequence was added synthetically to slow enzymatic degradation and extend the half-life of the compound in intranasal delivery.
Selank is Thr-Lys-Pro-Arg-Pro-Gly-Pro. Its active core is tuftsin, a tetrapeptide derived from the Fc region of human immunoglobulin G heavy chain. Selank also carries the Pro-Gly-Pro stability tail at the C-terminus. The shared tail is a synthetic engineering choice, not a sign of structural or pharmacological similarity between the active cores.
Both compounds emerged from Russian Academy of Sciences research in the late 1980s and 1990s, with Myasoedov and collaborators as key contributors to both programs. Semax is registered in Russia and Ukraine for ischemic stroke and certain cognitive and attention disorders. Selank is registered in Russia for generalized anxiety disorder and neurasthenia. Neither holds approval from the FDA, EMA, or Indonesian BPOM as of mid-2026.
Mechanism: neurotrophin signaling vs GABAergic modulation
Semax acts primarily through neurotrophin pathways. A 2009 rat study (PMID 19662538) measured NGF and BDNF gene expression in the hippocampus, frontal cortex, and retina of male Wistar rats at time points from 20 minutes to 24 hours after Semax administration. Both neurotrophins showed altered expression across brain regions over that time course, with the hippocampus responding earlier than the cortex. The temporal pattern of BDNF induction in the hippocampus aligns with the memory consolidation window observed in rodent learning models treated with Semax.
Semax also activates monoaminergic circuits. A 2006 rodent study (PMID 16362768) found that Semax at 0.1 mg/kg increased dopamine turnover in the frontal cortex and striatum and raised serotonin levels in the brainstem. Both effects are consistent with the improvements in attention and motivation that researchers observe in rodent behavioral assays.
Selank works through a different set of targets. A 2019 review of Selank's molecular pharmacology (PMID 30255741) identified subtype-selective, concentration-dependent allosteric modulation of GABA-A receptors as the primary mechanism of its anxiolytic effect. The compound enhances GABA-A receptor activity without binding at the classical benzodiazepine site, which may account for the absence of benzodiazepine-typical side effects in clinical reports.
A 2017 cell study (PMID 28293190) tested Selank in IMR-32 human neuroblastoma cells alongside GABA and olanzapine. Selank altered mRNA expression of GABA-A receptor subunit genes including GABRA1, GABRA5, and GABRB1 at concentrations from 10-8 to 10-12 M. The gene expression profile differed from both GABA and olanzapine tested under identical conditions, which argues for a receptor-specific rather than non-specific mechanism.
A second Selank mechanism involves enkephalin catabolism. Selank inhibits the enzymes that break down endogenous enkephalins in blood plasma, extending their half-life. Zozulya et al. (PMID 11550013, 2001) documented shortened enkephalin half-life and reduced total enkephalinase activity in patients with generalized anxiety disorder and found that Selank corrected both, which the authors proposed as one mechanism underlying its anxiolytic activity.
What the research shows
Semax has more indexed clinical evidence than Selank, though neither compound has been studied in a Western-registered randomized controlled trial. A 2004 clinical study in 187 patients with cerebrovascular insufficiency (PMID 15792140) found that Semax stabilized disease progression, reduced the frequency of transient ischemic attacks, and improved clinical scores compared to baseline. A 2018 study (PMID 29798983) enrolled 110 post-stroke patients (43 men, 67 women; mean age 58.0 years) and assigned them to early or late rehabilitation with or without Semax. The subgroup receiving early rehabilitation alongside Semax showed the largest plasma BDNF increase and the greatest improvement in Barthel index functional independence scores. The finding supports earlier observations connecting circulating BDNF levels to motor recovery after ischemic stroke.
For Selank, the most relevant human data comes from a 2008 clinical study (PMID 18577961) in patients with generalized anxiety disorder and neurasthenia. After 14 days of Selank treatment, investigators found normalization of the Th1/Th2 cytokine balance and reported anxiolytic effects described as comparable to low-dose benzodiazepines. The authors noted no sedation, cognitive impairment, or signs of dependence. Selank's effect on enkephalin metabolism in anxiety patients, documented by Zozulya et al. in 2001, provides a biochemical basis for that clinical picture.
Two limitations apply to both compounds. First, nearly all human data comes from Russian institutions, with no independently conducted replication in other countries. Second, the animal literature, though substantial, originates primarily from the same research groups that developed both compounds. These constraints do not invalidate the findings, but they are relevant to how much weight any single study should carry in a research decision.
Semax vs Selank at a glance
| Feature | Semax | Selank |
|---|---|---|
| Sequence | Met-Glu-His-Phe-Pro-Gly-Pro | Thr-Lys-Pro-Arg-Pro-Gly-Pro |
| Active core derived from | ACTH fragment (ACTH 4-7) | Tuftsin (IgG Fc region) |
| Primary mechanism | BDNF/NGF upregulation; dopamine and serotonin activation | GABA-A allosteric modulation; enkephalinase inhibition |
| Clinical registration in Russia | Ischemic stroke; cognitive and attention disorders | Generalized anxiety disorder; neurasthenia |
| Delivery in indexed research | Intranasal drops (registered 0.1% formulation) | Intranasal drops (registered 0.15% formulation) |
| Indexed human data | 2 studies: n=187 (CVD); n=110 (stroke) | 1 study: GAD/neurasthenia cohort, 14 days |
| Western RCT registration | None as of mid-2026 | None as of mid-2026 |
| Dependence profile | No dependence reported in published literature | Explicitly differentiated from benzodiazepines; no dependence reported |
Research protocol considerations
The registered Russian clinical formulations use intranasal delivery: 0.1% solution for Semax, 0.15% for Selank. Subcutaneous injection protocols appear in practitioner case reports and non-indexed literature, but this route was not used in the indexed human studies cited above. Researchers designing protocols should note that the human evidence base is built on intranasal administration data.
Both are synthetic linear heptapeptides. Standard handling applies: lyophilized powder at -20°C for long-term storage, reconstituted solutions at 2-8°C, and use within 14-21 days when reconstituted with bacteriostatic water. For researchers in Bali and across Indonesia, ambient temperatures routinely exceed 28°C year-round, which will degrade unrefrigerated solutions within hours. Active refrigeration from the point of receipt through use is not optional in ICH Zone IV conditions. The lyophilized peptide storage guide covers this in detail, including a practical two-tier cold storage setup for the tropics.
For syringe volume calculations, the peptide dosing calculator handles both compounds. Enter vial mass, reconstitution volume, and target dose in micrograms per kilogram to get the draw volume in U-100 syringe units.
No indexed peer-reviewed study has examined Semax and Selank in combination. The receptor systems involved (neurotrophin/monoamine vs GABA/enkephalin) do not overlap, but non-overlapping mechanisms do not establish additive or safe combined use without experimental evidence. For deeper background on Semax's neuroprotection and cognition literature, the Semax research overview covers the full body of animal and human studies. Both compounds are available in the compounds section of the catalog.