Semax vs Selank: what the published research shows

At a glance

One design idea, two starting points

Short natural peptides are broken down quickly by blood enzymes. The Institute of Molecular Genetics came up with a neat solution: take a short active fragment and attach a Pro-Gly-Pro tail to protect it. Semax starts from a fragment of the hormone ACTH; Selank starts from tuftsin, a fragment of an antibody protein. In rat blood, Semax proved more stable than the related ACTH(4-10) fragment against most of the enzymes involved, although an aminopeptidase still trimmed its first two amino acids.

Apart from the shared tail, the two molecules are unrelated. Their first four amino acids come from different proteins and the research on each has followed a different path.

Semax in the research

Most Semax research centres on brain-derived neurotrophic factor (BDNF), a protein involved in how nerve cells grow and form connections. In rats, a single intranasal dose produced a maximum 1.4-fold rise in BDNF protein in the hippocampus, a 1.6-fold rise in activation of its receptor trkB, and a 3-fold rise in BDNF mRNA. A separate study found specific, high-affinity binding sites for Semax in membranes from the rat basal forebrain, where BDNF also rose within three hours.

The other main thread is cerebral ischaemia, where blood flow to part of the brain is cut off. In a rat model, Semax changed the expression of 394 genes 24 hours after the injury compared with saline, damping inflammation-related genes and raising neurotransmission-related genes.

Semax has also been studied in people. Russian researchers ran clinical studies in stroke patients and published them in Russian. A 1997 study compared 30 patients given Semax with 80 patients on standard treatment, and a 2018 study followed 110 patients in groups with and without Semax.

Selank in the research

Selank research has focused on the GABA system, the brain's main calming signalling pathway and the target of benzodiazepines. In radioligand binding studies on brain membranes, Selank behaved as a positive allosteric modulator of GABA binding, meaning it changed how strongly GABA bound rather than binding in its place. In rats, Selank changed the expression of 45 of 84 neurotransmission-related genes in the frontal cortex within an hour, with a pattern that correlated with the changes produced by GABA itself.

Because its starting point is tuftsin, which has immune functions, Selank has also been studied in immune tissue. In mouse spleen, a single dose changed the expression of 34 of 84 inflammation-related genes.

In people, Russian researchers compared Selank with benzodiazepines in anxiety disorders: one study compared it with medazepam (30 and 32 patients), and another compared it with phenazepam in 60 patients. Both were published in Russian. A 2020 brain-imaging study in 52 healthy volunteers then compared Selank, Semax and placebo, and found differences in resting activity of the amygdala, a brain region involved in processing emotion.

Where the research stands

Semax has more than 30 years of published laboratory research, and Selank is a newer research area. Most clinical work so far comes from Russia, so larger international trials are the obvious next step for both. When FDA staff reviewed Semax in May 2026, they found that the clinical evidence was not yet enough to establish effectiveness or safety, and that no human pharmacokinetic studies were available. A 2021 review in the Journal of Clinical Pharmacology noted that Selank also still needs more study.

A 2022 review of peptide medicines developed in Russia lists Semax, classed as a nootropic, and Selank, classed as an anxiolytic, among 14 peptide products registered there. Outside Russia, both are research compounds rather than approved medicines, including in Australia. In the US, FDA staff recommended against adding Semax to the list of substances pharmacies can use for compounding; the FDA has not issued a final decision, and Selank was not reviewed.

Neither peptide is named on the WADA Prohibited List. However, WADA's S0 category bans any substance with no current approval by a government health regulator for human therapeutic use. Both are registered in Russia, so whether S0 applies has not been settled. Anyone subject to anti-doping testing should treat both with caution.

Sources

• Deigin et al., Pharmaceutics (2022) — Development of peptide biopharmaceuticals in Russia (lists Semax and Selank among 14 registered peptide products)
• Potaman et al., Biochem Biophys Res Commun (1991) — N-terminal degradation of ACTH(4-10) and Semax by rat blood enzymes
• Dolotov et al., J Neurochem (2006) — Semax binds specifically and increases BDNF protein in rat basal forebrain
• Dolotov et al., Brain Res (2006) — Semax regulates BDNF and trkB expression in the rat hippocampus
• Filippenkov et al., Genes (2020) — Semax and the rat brain transcriptome after ischaemia-reperfusion
• Gusev et al., Zh Nevrol Psikhiatr (1997) — Semax in the acute period of ischaemic stroke (in Russian)
• Gusev et al., Zh Nevrol Psikhiatr (2018) — Semax at different stages of ischaemic stroke (in Russian)
• US FDA — Briefing document: evaluation of Semax-related bulk drug substances (May 2026)
• Vyunova et al., Protein Pept Lett (2018) — Molecular aspects of Selank activity: allosteric modulation of GABA binding
• Volkova et al., Front Pharmacol (2016) — Selank affects expression of genes involved in GABAergic neurotransmission
• Kolomin et al., Regul Pept (2011) — Inflammation-related gene expression in mouse spleen under Selank
• Zozulia et al., Zh Nevrol Psikhiatr (2008) — Selank compared with medazepam in generalised anxiety disorder and neurasthenia (in Russian)
• Medvedev et al., Zh Nevrol Psikhiatr (2014) — Selank compared with phenazepam in anxiety disorders (in Russian)
• Panikratova et al., Dokl Biol Sci (2020) — Resting-state fMRI study of Selank and Semax in 52 healthy participants
• Doyno & White, J Clin Pharmacol (2021) — GABA-acting sedative-hypnotics, including Selank
• WADA — The Prohibited List
• PubChem — Semax (CID 9811102) and Selank (CID 11765600)