Compound research
Selank: research overview
Selank is a synthetic heptapeptide (Thr-Lys-Pro-Arg-Pro-Gly-Pro) designed at the Institute of Molecular Genetics of the Russian Academy of Sciences as an analogue of the endogenous peptide tuftsin. It has been studied, largely by Russian research groups, for its interaction with GABA receptor signalling, its inhibition of enkephalin-degrading enzymes and its effects on gene expression, in in-vitro assays, rodent models and clinical work in Russia.1–5
Mechanism at a glance
- GABA receptors (allosteric modulation)Reported in radioligand assays on brain membranes to act as a positive allosteric modulator of [3H]GABA binding. The authors proposed this as a possible basis of its activity.1, 2
- Enkephalin-degrading enzymesInhibited the enzymatic breakdown of enkephalin in plasma in vitro. The study authors proposed this as a possible mechanism.3
- Neurotransmission gene expressionAltered the expression of genes involved in GABAergic and other neurotransmission in rat frontal cortex.1
- Diazepam and other benzodiazepinesJoint effects examined in [3H]GABA binding assays and in a rat chronic mild stress model.2, 4
The cited authors present GABA receptor modulation and enkephalinase inhibition each as a possible mechanism. These studies do not describe how the two pathways relate.1–3
What it is
Selank is a synthetic seven-amino-acid peptide. It is based on tuftsin, the short Thr-Lys-Pro-Arg fragment of the human immunoglobulin G heavy chain, extended at the C-terminus by a Pro-Gly-Pro sequence. It was designed and produced at the Institute of Molecular Genetics, Russian Academy of Sciences, in cooperation with the V.V. Zakusov Research Institute of Pharmacology. A 2021 US review grouped it with other agents described as having GABAergic mechanisms.1, 6
How it acts
Two main mechanisms have been proposed in the literature: modulation of GABA receptor signalling and inhibition of enzymes that break down enkephalins. Effects on gene expression have also been studied.1–3
GABAergic signalling
In radioligand binding studies using brain cell membranes, Selank was reported to act as a positive allosteric modulator of [3H]GABA binding. Its joint effect with some benzodiazepines on GABA binding was described as non-additive. Selank was also reported to block the modulatory activity of diazepam and olanzapine. The authors suggested that its binding site is not the same as theirs but may partly overlap.2
Enkephalin-degrading enzymes
In vitro, Selank inhibited the enzymatic breakdown of enkephalin in plasma. In this assay it was reported to be more potent than the peptidase inhibitors bacitracin and puromycin. The authors proposed enkephalinase inhibition as a possible mechanism of its activity.3
Gene expression
In rats, real-time PCR analysis of a panel of 84 neurotransmission-related genes in the frontal cortex found expression changes at two time points after exposure to Selank or GABA. At the earlier time point, the pattern of changes correlated positively with that seen after GABA. The authors linked these findings to possible allosteric modulation of the GABAergic system.1
Research status
Most of the studies cited here come from Russian research groups. The evidence spans in-vitro assays, rodent studies and clinical work published in Russian.1–5
Animal models
In rats, Selank alone and together with diazepam was studied in the elevated plus maze, both with and without unpredictable chronic mild stress.4
Human studies
A clinical study in Russia, indexed in PubMed as a randomised controlled trial, compared Selank with medazepam in patients with generalised anxiety disorder and neurasthenia. It examined psychometric rating scales and the half-life of leu-enkephalin in serum.5
Review from the United States
A 2021 review in the Journal of Clinical Pharmacology, by authors based in the United States, described Selank as a poorly studied Russian drug.6
Published research at a glance
- In vitro
Inhibition of enkephalin-degrading enzymes in plasma
- In vitro
Allosteric modulation of [3H]GABA binding in brain membrane preparations, alone and with benzodiazepines
- Animal model
Expression of neurotransmission-related genes in rat frontal cortex, compared with GABA
- Animal model
Anxiety-related behaviour in the elevated plus maze under unpredictable chronic mild stress, alone and with diazepam
- Clinical trial
Comparison with medazepam in generalised anxiety disorder and neurasthenia, using rating scales and serum enkephalin measures
- Review
GABA-receptor-acting sedative-hypnotic agents, including Selank, and their availability to US consumers
Research status: A 2021 review in the Journal of Clinical Pharmacology stated that Selank was being sold to US consumers as a dietary supplement.6
Technical specifications
- Molecular formula
- C33H57N11O9
- Molecular weight
- 751 Da
- CAS number
- 129954-34-3
References
- Volkova A, Shadrina M, Kolomin T, et al. Selank Administration Affects the Expression of Some Genes Involved in GABAergic Neurotransmission. Frontiers in Pharmacology (2016). doi:10.3389/fphar.2016.00031
- Vyunova TV, Andreeva L, Shevchenko K, Myasoedov N. Peptide-based Anxiolytics: The Molecular Aspects of Heptapeptide Selank Biological Activity. Protein and Peptide Letters (2018). doi:10.2174/0929866525666180925144642
- Zozulya AA, Kost NV, Yu Sokolov O, et al. The inhibitory effect of Selank on enkephalin-degrading enzymes as a possible mechanism of its anxiolytic activity. Bulletin of Experimental Biology and Medicine (2001). doi:10.1023/a:1017979514274
- Kasian A, Kolomin T, Andreeva L, et al. Peptide Selank Enhances the Effect of Diazepam in Reducing Anxiety in Unpredictable Chronic Mild Stress Conditions in Rats. Behavioural Neurology (2017). doi:10.1155/2017/5091027
- Zozulia AA, Neznamov GG, Siuniakov TS, et al. Efficacy and possible mechanisms of action of a new peptide anxiolytic selank in the therapy of generalized anxiety disorders and neurasthenia [Article in Russian]. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova (2008). PubMed 18454096
- Doyno CR, White CM. Sedative-Hypnotic Agents That Impact Gamma-Aminobutyric Acid Receptors: Focus on Flunitrazepam, Gamma-Hydroxybutyric Acid, Phenibut, and Selank. Journal of Clinical Pharmacology (2021). doi:10.1002/jcph.1922
Literature summary compiled on 15 October 2026.