Abstract
An in-depth review of Selank, the synthetic heptapeptide anxiolytic derived from tuftsin, covering its molecular design, GABAergic mechanisms, clinical research in anxiety disorders, immunomodulatory properties, and cognitive enhancement effects.
Selank is a synthetic heptapeptide with the sequence Thr-Lys-Pro-Arg-Pro-Gly-Pro, created by adding the Pro-Gly-Pro stabilizing tripeptide to tuftsin (Thr-Lys-Pro-Arg), a naturally occurring immunomodulatory tetrapeptide derived from the heavy chain of immunoglobulin G. Developed at the Institute of Molecular Genetics of the Russian Academy of Sciences—the same laboratory that created Semax—Selank was designed to combine the immunostimulatory properties of tuftsin with enhanced anxiolytic and nootropic effects while achieving sufficient metabolic stability for clinical use.
The molecular weight of Selank is approximately 751 daltons. Like Semax, the Pro-Gly-Pro C-terminal extension provides critical resistance to enzymatic degradation, extending the biological half-life well beyond that of native tuftsin. This structural engineering approach, pioneered by the Myasoedov laboratory, represents a consistent strategy for converting biologically active but rapidly degraded endogenous peptides into therapeutically viable drug candidates.
The anxiolytic mechanism of Selank involves multiple interacting pathways, with modulation of the GABAergic system being the most extensively characterized. Research has demonstrated that Selank increases GABA concentrations in the brain, likely through inhibition of enzymes that degrade enkephalins—the brain's endogenous opioid peptides that modulate pain perception, emotional responses, and anxiety. By stabilizing enkephalins from enzymatic breakdown, Selank indirectly enhances GABAergic inhibitory tone. Unlike benzodiazepines, which bind directly to GABA-A receptor allosteric sites and can cause sedation, tolerance, and dependence, Selank's indirect GABAergic enhancement produces anxiolysis without significant sedation or addiction potential.
Genomic studies have revealed that Selank influences the expression of a remarkably broad set of genes. Research documented that Selank modulates 84 genes in the hippocampus, with particular effects on genes involved in GABAergic neurotransmission, serotonergic signaling, and inflammation. Specifically, Selank upregulates the expression of GABA transaminase and multiple GABA receptor subunits while also modulating serotonin transporter expression and serotonin receptor subtypes. These dual GABAergic-serotonergic effects provide a neurochemical basis for Selank's combined anxiolytic and antidepressant-like activities.
Clinical trials of Selank have focused primarily on generalized anxiety disorder (GAD) and neurasthenic conditions. A pivotal clinical study compared Selank with medazepam (a benzodiazepine anxiolytic) in patients with GAD. Both treatments produced significant anxiolytic effects, but Selank demonstrated notable advantages in the cognitive domain: patients receiving Selank showed improvements in attention and memory, while those receiving medazepam showed the expected cognitive impairment associated with benzodiazepine use. This dissociation between anxiolysis and cognitive impairment is one of Selank's most clinically significant features.
Additional clinical research in patients with anxiety and neurasthenia demonstrated that intranasal Selank at doses of 450 micrograms per day for 14 days produced significant reductions in anxiety scores on standardized scales, improvements in asthenia and mood, and enhanced cognitive function. The anxiolytic effect was observed as early as day 3 of treatment and reached full magnitude by day 7 to 10, persisting throughout the treatment course and for a period after discontinuation.
The immunomodulatory properties of Selank reflect its tuftsin heritage and represent a unique dual-function profile not seen in conventional anxiolytics. Tuftsin is a well-established immunostimulant that enhances phagocytic activity, natural killer cell function, and cytokine production. Selank retains these immunomodulatory properties while adding anxiolytic and nootropic effects. Research has shown that Selank influences the balance between pro-inflammatory and anti-inflammatory cytokines, with evidence suggesting a shift toward anti-inflammatory and immunoregulatory states. This property may be particularly relevant for conditions where immune dysregulation contributes to anxiety and cognitive impairment, such as chronic stress, autoimmune conditions, and viral infections.
Of particular clinical interest, Selank has been investigated as an adjunctive treatment for hepatitis C, where its immunomodulatory properties may complement antiviral therapy. A clinical study demonstrated that Selank improved immune parameters and psychological wellbeing in hepatitis C patients, suggesting applications beyond traditional psychiatric use.
Selank also influences the expression of neurotrophic factors, though less potently than Semax. Studies have documented modest increases in BDNF expression following Selank treatment, which may contribute to its cognitive-enhancing effects and potential neuroprotective properties. The combination of anxiolytic, immunomodulatory, and neurotrophic mechanisms makes Selank a uniquely multifunctional peptide.
Regarding safety, Selank has demonstrated an excellent tolerability profile across clinical trials and extensive post-marketing experience in Russia, where it received regulatory approval in 2009. It is available as a 0.15 percent intranasal solution. The most commonly reported side effects are mild nasal irritation and occasional transient headache. Importantly, Selank does not produce sedation, psychomotor impairment, tolerance, or withdrawal symptoms—key limitations of benzodiazepine anxiolytics. No physical dependence or addiction liability has been observed in either animal or human studies.
N-Acetyl Selank and N-Acetyl Selank Amidate represent modified forms available through research chemical suppliers. These modifications enhance metabolic stability through N-terminal acetylation and/or C-terminal amidation, potentially improving CNS penetration and extending the duration of action. Published data on these specific analogs is limited compared to the parent compound.
Selank remains a prescription medication in Russia and is not approved in Western jurisdictions. It is available internationally as a research chemical, where it has garnered significant interest in the nootropics and biohacking communities for its anxiolytic effects without cognitive impairment.
