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Selank (TP-7 / Tuftsin Analog) Evidence Grade: A-

Selank is a synthetic heptapeptide (Thr-Lys-Pro-Arg-Pro-Gly-Pro) derived from the endogenous immunopeptide tuftsin with a stabilizing Pro-Gly-Pro C-terminal extension. Developed at the Institute of Molecular Genetics of the Russian Academy of Sciences alongside Semax, Selank is approved in Russia as a prescription anxiolytic and nootropic agent. It produces anti-anxiety effects comparable to benzodiazepines without sedation, cognitive impairment, or addiction potential.

Selank's unique pharmacological profile combines anxiolytic, nootropic, and immunomodulatory effects in a single compound, reflecting its dual heritage from the tuftsin immunopeptide parent and the neurotropic design principles applied during development. It modulates GABAergic, serotonergic, and dopaminergic neurotransmission while simultaneously enhancing innate immune function through phagocyte activation and cytokine regulation.

Class: Anxiolytic Peptide
Formula: C33H57N9O9
MW: 751.87 Da
CAS: 129954-34-3
Half-Life: Several hours (IN)
Route: Intranasal / SubQ
Approved: Russia (Rx)
Grade: A- (Clinical Use in Russia)

Overview & Introduction

Selank was developed using the same pharmacological design strategy as Semax: take a biologically active endogenous peptide fragment and add a Pro-Gly-Pro C-terminal extension to increase enzymatic stability and extend biological half-life. For Selank, the starting point was tuftsin (Thr-Lys-Pro-Arg), a tetrapeptide naturally produced by enzymatic cleavage of immunoglobulin G (IgG) in the spleen.

Tuftsin itself is an endogenous immunostimulant that activates phagocytosis, natural killer cell activity, and monocyte/macrophage function. The Pro-Gly-Pro extension not only stabilized the molecule but unexpectedly conferred potent anxiolytic and nootropic properties beyond the parent peptide's immune effects. This serendipitous discovery led to Selank's development as a dual-action compound with both neurotropic and immunotropic activities.

The anxiolytic mechanism involves allosteric modulation of GABA receptors, enhancement of serotonergic neurotransmission, and inhibition of enkephalin-degrading enzymes. Unlike benzodiazepines, which directly potentiate GABA-A receptor chloride channel activity, Selank appears to act as a positive allosteric modulator that increases GABA receptor sensitivity to endogenous GABA. This indirect modulation produces anxiolysis without the sedation, ataxia, cognitive impairment, or dependence associated with direct GABA-A agonism.

Selank received regulatory approval in Russia and has been used clinically since 2009. It is available as a 0.15% nasal spray indicated for generalized anxiety disorder, neurasthenia, and as an adjunctive treatment for anxiety-related cognitive impairment. Russian clinical literature describes Selank's anxiolytic and cognitive properties in studies of generalized anxiety disorder and neurasthenia. Selank is not approved by the FDA or EMA for any indication; all content on this page reflects published research literature and is for research purposes only.

History & Discovery

1980s

Tuftsin characterization. Tuftsin was established as an endogenous immunostimulatory tetrapeptide derived from IgG. Its role in phagocyte activation and innate immunity was well characterized.

1990s

Selank synthesis. Scientists at the Institute of Molecular Genetics added the Pro-Gly-Pro extension to tuftsin, creating TP-7 (Selank). The stabilized analog demonstrated unexpectedly potent anxiolytic and nootropic effects in animal behavioral models.

2000-2008

Clinical development. Extensive preclinical and clinical studies characterized Selank's anxiolytic efficacy, GABAergic mechanism, immunomodulatory effects, and safety profile. Phase II/III clinical trials compared Selank to benzodiazepines and placebo.

2009

Russian regulatory approval. Selank received approval in Russia as a 0.15% intranasal solution for anxiety and neurasthenia. Made available by prescription.

2010-Present

International research. Selank gained global research attention for its unique non-sedating anxiolytic profile. Studies expanded into antiviral effects, gene expression modulation, and PTSD research.

Mechanism of Action

GABA Receptor Modulation

Radioligand-binding studies show Selank acts as a positive allosteric modulator of the GABA receptor, and separately, real-time PCR studies in rat frontal cortex found Selank altered expression of numerous genes involved in GABAergic neurotransmission. Selank's effects on GABA binding partially overlap with, but are distinct from, those of benzodiazepines such as diazepam. This produces anxiolysis without the excessive inhibition typical of direct GABA-A agonists, preserving normal cognitive function and motor coordination.

Serotonergic System Enhancement

Selank modulates serotonin (5-HT) metabolism and receptor sensitivity, particularly in limbic structures involved in anxiety processing (amygdala, hippocampus, prefrontal cortex). It influences the balance between serotonin synthesis, release, and reuptake, contributing to mood stabilization and anxiolysis. This serotonergic mechanism complements the GABAergic effects and may account for the compound's antidepressant-like properties.

Enkephalin System Modulation

Rather than increasing enkephalin production, Selank has been shown to inhibit enkephalin-degrading enzymes in human blood plasma, prolonging the half-life of endogenous leu-enkephalin. Enkephalins modulate pain perception, stress responses, and emotional processing through delta-opioid receptors. This endogenous opioid modulation contributes to stress resilience and emotional regulation without producing opioid-like euphoria or dependence.

Immune Modulation (Tuftsin Heritage)

Selank retains and enhances the immunostimulatory properties of its parent peptide tuftsin. It activates phagocytosis, increases natural killer cell activity, modulates cytokine production, and influences antiviral defense pathways. In vitro and in vivo studies have demonstrated antiviral activity against influenza A virus, associated with induction of interferon-alpha gene expression. This immune modulation is unique among anxiolytic compounds.

Research Applications

Generalized Anxiety Disorder

Primary clinical indication. Selank's non-sedating anxiolytic profile makes it suitable for daytime anxiety management where cognitive function must be preserved.

Cognitive Enhancement Under Stress

Selank improves cognitive performance (attention, memory, processing speed) specifically under stress conditions. Its dual anxiolytic-nootropic profile restores stress-impaired cognition.

Immune System Research

The tuftsin-derived immune effects make Selank unique for studying the neuro-immune interface. It is investigated for combined anxiolytic and immunomodulatory applications.

Antiviral Research

Selank has demonstrated antiviral activity in vitro and in vivo against influenza A (H3N2). The mechanism involves induction of interferon-alpha (IFN-alpha) gene expression and innate immune pathway activation.

Clinical Evidence

Anxiolytic Efficacy in GAD and Neurasthenia

Zozulia et al. (2008) studied 62 patients with generalized anxiety disorder (GAD) and neurasthenia, comparing Selank (30 patients, 0.15% intranasal) to the benzodiazepine medazepam (32 patients) using the Hamilton, Zung, and CGI scales. Both treatments produced comparable anxiolytic effects, but Selank additionally showed antiasthenic and psychostimulant effects. The study also measured serum leu-enkephalin activity, which increased during Selank treatment and correlated with symptom improvement.

PMID: 18454096

GABA Receptor Modulation

Correction: This page previously cited a "Seredenin et al. (1998)" paper (PMID 9830143) for Selank's benzodiazepine-receptor mechanism and a flumazenil-blockade finding; that PMID actually belongs to an unrelated paper on RNA extraction from fermented foods, and we could not locate any genuine PubMed record matching that citation. The best-supported, verifiable study on this mechanism is Vyunova et al. (2018), which used radioligand binding assays to show Selank acts as a positive allosteric modulator of the GABA receptor. Selank could block some of the modulatory activity of diazepam and olanzapine, suggesting its binding site partially, but not fully, overlaps with the benzodiazepine site.

PMID: 30255741

Gene Expression Effects

Correction: This page previously cited a "Kost et al. (2001)" paper (PMID 11515319) claiming Selank increases proenkephalin gene expression in the hippocampus; that PMID actually belongs to an unrelated paper on hypertonic saline resuscitation in a swine gunshot-wound model, and we could not locate any genuine PubMed record supporting the specific claim of proenkephalin upregulation. A genuine, verifiable study is Volkova et al. (2016), which used real-time PCR in rat frontal cortex and found Selank altered expression of numerous genes involved in GABAergic neurotransmission, consistent with allosteric modulation of the GABA system. Separately, Zozulya et al. (2001, PMID 11550013) showed Selank inhibits enkephalin-degrading enzymes in blood plasma—the better-supported link between Selank and the enkephalin system.

PMID: 26924987

Antiviral Activity

Ershov et al. (2009) evaluated Selank's antiviral properties against influenza A (H3N2, strain A/Aichi 2/68) in vitro and in vivo. Selank most effectively suppressed viral replication when applied preventively (before infection) and improved survival in infected animals. In vivo, Selank induced expression of interferon-alpha (IFN-alpha) without affecting IL-4, IL-10, or TNF-alpha, suggesting a mechanism involving modulation of Th1/Th2/Treg cytokine balance.

PMID: 19882898

Dosing Protocols (Research Context)

Note: Selank is approved in Russia but not FDA/EMA-approved.

FormDoseFrequency
0.15% Nasal Solution250-500 mcg/day (2-3 drops per nostril)3 times daily
Subcutaneous Injection250-750 mcg1-2 times daily

Standard protocols run 14-21 days. Cycles can be repeated after 1-2 week intervals. No tapering required upon discontinuation.

Administration & Reconstitution

Nasal Spray (Primary)

Pre-mixed 0.15% solution. Administer drops intranasally, alternating nostrils. Provides rapid CNS access via olfactory pathways.

Injectable

VialBAC WaterConcentration
5 mg2 mL2.5 mg/mL
  • Reconstitute gently; inject subcutaneously
  • Intranasal route preferred for anxiolytic effects

Side Effects & Safety Profile

Selank has an outstanding safety profile with no significant adverse events in 15+ years of clinical use in Russia.

Rare/Mild

  • Mild nasal irritation
  • Occasional fatigue (uncommon)

Key Safety Features

  • No sedation
  • No addiction or dependence
  • No withdrawal or rebound anxiety
  • No cognitive impairment
  • No motor coordination effects

Stacking & Combinations

Selank + Semax

The flagship Russian nootropic combination. Semax provides BDNF-driven cognitive enhancement while Selank delivers anxiolysis and stress resilience. Together they optimize cognitive performance under pressure.

Selank + BPC-157

For gut-brain axis research: Selank's anxiolytic/serotonergic effects complement BPC-157's gut healing and dopaminergic modulation. Both compounds influence the gut-brain connection through different mechanisms.

Selank + Thymosin Alpha-1

For combined immune and neurological support: Selank provides tuftsin-derived immune activation plus anxiolysis, while Thymosin Alpha-1 delivers T-cell immune enhancement.

Storage & Stability

FormConditionsDuration
Nasal Solution (sealed)RefrigeratedUntil expiry
Nasal Solution (opened)Refrigerated30 days
LyophilizedRefrigerated24+ months
ReconstitutedRefrigerated21 days

Regulatory Status

  • Russia: Approved (2009) as prescription anxiolytic and nootropic. Available as 0.15% nasal solution.
  • United States: Not FDA-approved. Research peptide.
  • EU: Not EMA-approved.
  • WADA: Not currently prohibited.

Frequently Asked Questions

How does Selank compare to benzodiazepines?
Selank produces anxiolytic effects comparable to benzodiazepines in clinical studies, but without sedation, cognitive impairment, muscle relaxation, or addiction. It does not produce tolerance, physical dependence, or withdrawal symptoms. It also has nootropic properties, whereas benzodiazepines typically impair cognition.
What is tuftsin and why is Selank based on it?
Tuftsin is a naturally occurring tetrapeptide derived from IgG that functions as an endogenous immunostimulant. Selank was designed by adding a Pro-Gly-Pro extension to tuftsin, which stabilized the molecule and unexpectedly produced potent anxiolytic and nootropic effects beyond the parent peptide's immune modulation.
Is Selank addictive?
No. Selank has shown no addictive potential in any study. It does not produce euphoria, tolerance, dependence, or withdrawal symptoms. It can be discontinued abruptly without rebound anxiety.

References

  1. 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]. Zh Nevrol Psikhiatr Im S S Korsakova. 2008;108(4):38-48. PMID: 18454096
  2. Vyunova TV, Andreeva LN, Shevchenko KG, Myasoedov NF. "Peptide-based Anxiolytics: The Molecular Aspects of Heptapeptide Selank Biological Activity." Protein Pept Lett. 2018;25(10):914-923. PMID: 30255741
  3. Volkova A, Shadrina M, Kolomin T, et al. "Selank Administration Affects the Expression of Some Genes Involved in GABAergic Neurotransmission." Front Pharmacol. 2016;7:31. PMID: 26924987
  4. Zozulya AA, Kost NV, Sokolov OY, 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
  5. Ershov FI, Uchakin PN, Uchakina ON, et al. "Antiviral activity of immunomodulator Selank in experimental influenza infection." [Article in Russian]. Vopr Virusol. 2009;54(5):19-24. PMID: 19882898

Related Pages

Selank Compound Page

Concise compound overview

Selank Protocol Guide

Step-by-step protocol

Semax Wiki

Nootropic combination partner

Thymosin Alpha-1 Wiki

Immune support partner

Medical Disclaimer: This article is for educational and research purposes only. Selank is not FDA-approved. Consult a healthcare professional. See our full Medical Disclaimer.

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