Selank Research

Selank research occupies a particular niche in neuropeptide pharmacology: the study of a small synthetic peptide developed as a stable, anxiolytic-type regulator. Selank is a synthetic heptapeptide based on the natural immunopeptide tuftsin. Much of the interest in it concerns how it interacts with GABAergic signaling and related systems in the brain. This article summarizes research on Selank and anxiolytic peptide biology, most of it preclinical. It covers its structure, the mechanisms proposed for it, the cell and animal evidence, and the small body of human research. It states whether each finding comes from a cell, an animal, or a human study, and it describes what research has investigated rather than any outcome a reader should expect. Selank is a research compound and is not characterized here for human use.

What is Selank?

Selank is a synthetic heptapeptide with the sequence Thr-Lys-Pro-Arg-Pro-Gly-Pro, built from the endogenous tetrapeptide tuftsin. Tuftsin is the short Thr-Lys-Pro-Arg fragment derived from the heavy chain of immunoglobulin G. Selank extends that fragment at the C-terminus by three natural amino acids, Pro-Gly-Pro. That extension was added specifically to improve the molecule's metabolic stability and to give it a longer duration than the rapidly degraded parent peptide.

Selank was developed at the Institute of Molecular Genetics of the Russian Academy of Sciences. Selank derives from tuftsin, an immunomodulatory peptide, so it carries both neuropeptide and immune-related activities. That dual character is part of what makes its pharmacology complex.

The GABAergic angle

The link between Selank and GABAergic signaling is the most actively studied aspect of its mechanism. Volkova and colleagues reported in 2016 that administration of Selank changed the mRNA levels of several genes involved in GABAergic neurotransmission in the rat frontal cortex. That work was done in living animals, and the pattern of change correlated with the pattern produced by GABA itself. The authors concluded that one of Selank's possible molecular mechanisms is allosteric modulation of the GABAergic system. This is an in vivo (rat) finding, and a proposed mechanism rather than a confirmed one.^[1]

A follow-up study by Filatova and colleagues in 2017 tested the same question in cultured human IMR-32 neuroblastoma cells. Selank alone produced no change in the mRNA levels of the GABAergic genes studied. When it was combined with GABA, it suppressed most of the expression changes that GABA produced on its own. Taken together, these in vitro results suggest that Selank does not act directly on GABAergic gene transcription in isolated cells. The same in vitro results suggest it may instead modify the interaction of GABA with its receptors, which is consistent with the whole-animal effects being indirect.^[2] The two studies illustrate that the GABAergic mechanism of Selank is plausible but not fully resolved.

Vyunova and colleagues added a radioligand result in 2018. In radioligand binding assays on plasma membranes isolated from rat brain cells, Selank acted as a positive allosteric modulator of [3H]GABA binding. In those same assays it also blocked the modulatory activity of diazepam and olanzapine, and the peptide's binding site appeared distinct from the benzodiazepine binding site, though potentially partially overlapping with it.^[6]

Selank mechanism of action beyond GABA

A second, better-characterized strand concerns the endogenous opioid system. Zozulya and colleagues reported in 2001 that Selank inhibits enkephalin-degrading enzymes in vitro, dose-dependently slowing the enzymatic hydrolysis of plasma enkephalin and doing so more potently than the reference peptidase inhibitors bacitracin and puromycin.^[3] By slowing enkephalin breakdown, the peptide is thought to prolong endogenous enkephalin signaling rather than acting directly on opioid receptors.

Animal data support this strand. Sokolov and colleagues showed in 2002 that Selank produced an anxiolytic-type effect in the open-field test in a mouse strain prone to anxiety-like behavior. The peptide also increased the half-life of plasma enkephalin in that strain, whereas a different strain showed neither response.^[4]

A further strand concerns neurotrophic signaling: Inozemtseva and colleagues reported in 2008 that intranasal Selank regulated brain-derived neurotrophic factor (BDNF) expression in the rat hippocampus in vivo.^[5] That finding adds a neurotrophic dimension to the peptide's actions. Changes in monoamine-related gene expression were also reported in the rat gene-expression work above, indicating that Selank acts across more than one neurotransmitter system.^[1]

Preclinical behavioral findings

Behavioral pharmacology in rodents has characterized Selank as an anxiolytic-type compound with a profile distinct from classical sedatives. In the open-field test, Sokolov and colleagues reported an anxiolytic-type effect in anxiety-prone BALB/c mice at 100 μg/kg, with no corresponding behavioral change in C57Bl/6 mice.^[4]

The 2001 enzymology report characterizes Selank as attenuating behavioral anxiety reactions without the side effects typical of most anxiolytics, though that paper measured enzyme activity rather than behavior.^[3] Cognitive endpoints have also been examined: Semenova and colleagues reported in 2007 that Selank affected cognitive processes in rats following early-life damage to the brain's catecholamine system.^[7] These are animal model results and should not be extrapolated to human outcomes.

Human research

Selank is registered in Russia as non-prescription nasal drops, classed as an anxiolytic and held by JSC INPC Peptogen.^[8][15] It has no US approval, and FDA's page on bulk drug substances that may present significant safety risks in compounding lists selank acetate among substances previously in category 2 whose nominations were withdrawn, stating that FDA lacks important information regarding any safety issues raised by selank acetate administered to humans.^[9] Its human literature is a handful of Russian studies, and N. F. Myasoedov, of the institute that developed Selank, is an author on every human study described here.

The 2001 enzymology study above included a human biochemical observation: patients with generalized anxiety showed a shortened enkephalin half-life and reduced blood enkephalinase activity.^[3] A clinical study then compared Selank with the benzodiazepine medazepam in 62 patients with generalized anxiety disorder or neurasthenia, 30 on Selank and 32 on medazepam, rated on the Hamilton, Zung, and Clinical Global Impression scales.^[10] The authors reported similar anti-anxiety effects for the two drugs, with additional anti-asthenic and stimulant effects attributed to Selank. They also reported that the shortened leu-enkephalin half-life lengthened during Selank treatment, mostly in generalized anxiety disorder.

Medvedev and colleagues compared Selank with the benzodiazepine phenazepam in 60 patients with phobic anxiety and somatoform disorders, and reported an anti-anxiety effect that lasted a week after the last dose.^[11] In a second study, the same group compared phenazepam alone in 30 patients with phenazepam plus Selank in 40, and reported an earlier response on the Hamilton Depression Rating Scale and reduced severity of several phenazepam side effects with the combination.^[12] A further study reported shifts in the balance of Th1 and Th2 cytokines in the serum of patients with generalized anxiety disorder or neurasthenia after 14 days of Selank.^[13]

In healthy volunteers, a 2020 imaging study compared Selank, Semax, and placebo in 52 participants and reported changes in functional connectivity between the right amygdala and the right temporal cortex.^[14] The medazepam and phenazepam studies compared Selank with a benzodiazepine or added it to one, and none of the patient studies' abstracts describes a placebo arm. None of this establishes an outcome for any individual.

Limitations and research directions

Several limitations shape how this literature should be read. A large share of the work originates from a small network of affiliated Russian institutes, and much of it is published in Russian-language journals, which limits independent replication. The proposed mechanisms, GABAergic, enkephalinergic, neurotrophic and monoaminergic, are multiple and not fully reconciled. The contrast between the in vivo and in vitro GABAergic findings shows that the picture is still being worked out. The human studies are small, the abstracts of the patient studies describe no placebo arm, and N. F. Myasoedov is an author on every one of them.

Conclusion

Selank is best understood as a metabolically stabilized, tuftsin-derived heptapeptide studied as an anxiolytic-type neuropeptide. Its preclinical profile points to a multi-target mechanism, with action on the GABAergic system proposed but not fully resolved. The effect on enkephalin-degrading enzymes is better characterized, and both sit alongside behavioral data in animal models. Its clinical studies in anxiety disorders mostly compared it with or added it to benzodiazepines, and their abstracts describe no placebo arm; the one placebo-controlled human study described here was an imaging study in healthy volunteers.

References

1. 1

   Volkova A, Shadrina M, Kolomin T, Andreeva L, Limborska S, Myasoedov N, Slominsky P. Selank administration affects the expression of some genes involved in GABAergic neurotransmission. Front Pharmacol. 2016;7:31. PMID 26924987.
2. 2

   Filatova E, Kasian A, Kolomin T, Rybalkina E, Alieva A, Andreeva L, et al. GABA, Selank, and olanzapine affect the expression of genes involved in GABAergic neurotransmission in IMR-32 cells. Front Pharmacol. 2017;8:89. PMID 28293190.
3. 3

   Zozulya AA, Kost NV, Sokolov OYu, Gabaeva MV, Grivennikov IA, Andreeva LN, et al. The inhibitory effect of Selank on enkephalin-degrading enzymes as a possible mechanism of its anxiolytic activity. Bull Exp Biol Med. 2001;131(4):315-317. PMID 11550013.
4. 4

   Sokolov OYu, Meshavkin VK, Kost NV, Zozulya AA. Effects of Selank on behavioral reactions and activities of plasma enkephalin-degrading enzymes in mice with different phenotypes of emotional and stress reactions. Bull Exp Biol Med. 2002;133(2):133-135. PMID 12432865.
5. 5

   Inozemtseva LS, Karpenko EA, Dolotov OV, Levitskaya NG, Kamensky AA, Andreeva LA, et al. Intranasal administration of the peptide Selank regulates BDNF expression in the rat hippocampus in vivo. Dokl Biol Sci. 2008;421:241-243. PMID 18841804.
6. 6

   Vyunova TV, Andreeva L, Shevchenko K, Myasoedov N. Peptide-based anxiolytics: the molecular aspects of heptapeptide Selank biological activity. Protein Pept Lett. 2018;25(10):914-923. PMID 30255741.
7. 7

   Semenova TP, Kozlovskaya MM, Zakharova NM, Kozlovskii II, Zuikov AV. Effect of selank on cognitive processes after damage inflicted to the cerebral catecholamine system during early ontogeny. Bull Exp Biol Med. 2007;144(5):689-691. PMID 18683497.
8. 8

   Vidal Russian drug reference, entry for Selank (vidal.ru/drugs/selank__21568), retrieved 3 October 2026: Selank nasal drops 0.15%, registration ЛП-№(010951)-(РГ-RU) dated 15 July 2025, previous registration ЛСР-003338/09, holder JSC INPC Peptogen, ATC code N05BX (other anxiolytics), listed as non-prescription. vidal.ru
9. 9

   US Food and Drug Administration. "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks," content current as of 22 April 2026, listing selank acetate (TP-7) under "Bulk drug substances nominated but withdrawn" (substances previously in category 2 whose nominations the nominators withdrew); and Drugs@FDA, queried via api.fda.gov on 5 October 2026 for "Selank", "Selank acetate" and "TP-7" (substance name, generic name and active ingredient fields), no record under any of them. The FDA page was retrieved 3 October 2026. fda.gov
10. 10

    Zozulia AA, Neznamov GG, Siuniakov TS, Kost NV, Gabaeva MV, Sokolov OIu, et al. [Efficacy and possible mechanisms of action of a new peptide anxiolytic selank in the therapy of generalized anxiety disorders and neurasthenia]. Zh Nevrol Psikhiatr Im S S Korsakova. 2008;108(4):38-48. PMID 18454096. In Russian.
11. 11

    Medvedev VE, Tereshchenko ON, Israelian AIu, Chobanu IK, Kost NV, Sokolov OIu, Miasoedov NF. [A comparison of the anxiolytic effect and tolerability of selank and phenazepam in the treatment of anxiety disorders]. Zh Nevrol Psikhiatr Im S S Korsakova. 2014;114(7):17-22. PMID 25176261. In Russian.
12. 12

    Medvedev VE, Tereshchenko ON, Kost NV, Ter-Israelyan AY, Gushanskaya EV, Chobanu IK, Sokolov OY, Myasoedov NF. [Optimization of the treatment of anxiety disorders with selank]. Zh Nevrol Psikhiatr Im S S Korsakova. 2015;115(6):33-40. PMID 26356395. doi:10.17116/jnevro20151156133-40. In Russian.
13. 13

    Uchakina ON, Uchakin PN, Miasoedov NF, Andreeva LA, Shcherbenko VE, Mezentseva MV, et al. [Immunomodulatory effects of selank in patients with anxiety-asthenic disorders]. Zh Nevrol Psikhiatr Im S S Korsakova. 2008;108(5):71-75. PMID 18577961. In Russian.
14. 14

    Panikratova YR, Lebedeva IS, Sokolov OY, Rumshiskaya AD, Kupriyanov DA, Kost NV, Myasoedov NF. Functional connectomic approach to studying Selank and Semax effects. Dokl Biol Sci. 2020;490(1):9-11. PMID 32342318. doi:10.1134/S001249662001007X.
15. 15

    State Register of Medicines (GRLS), Ministry of Health of the Russian Federation, entry for Selank nasal drops 0.15%, retrieved 5 October 2026: registration holder JSC INPC Peptogen, pharmacotherapeutic group anxiolytic (tranquilizer), ATC code N05BX, dispensed without prescription. grls.rosminzdrav.ru