Selank is a synthetic heptapeptide (sequence: Thr-Lys-Pro-Arg-Pro-Gly-Pro) developed by the Institute of Molecular Genetics of the Russian Academy of Sciences. It is a structural analog of the endogenous peptide tuftsin (Thr-Lys-Pro-Arg), to which a tripeptide sequence (Pro-Gly-Pro) has been added to the C-terminus to improve metabolic stability and duration of action[1].
Selank is characterized as a "daytime" anxiolytic because it exhibits anxiety-reducing properties without the sedative, muscle-relaxant, or cognitive-impairing side effects typically associated with classical benzodiazepines. In addition to its anxiolytic effects, Selank has been shown to possess nootropic (cognitive-enhancing) and immunomodulatory properties, making it a unique compound in the field of peptide pharmacology and longevity research[2][3].
¶ Mechanism of Action
Selank operates through a distinct set of mechanisms that differ significantly from traditional anxiolytics. While benzodiazepines act as direct allosteric modulators of GABA-A receptors, Selank appears to modulate the central nervous system through gene expression regulation and neurotrophic factor support.
¶ 1. Regulation of GABAergic Gene Expression
Research indicates that Selank modulates the expression of genes involved in GABAergic neurotransmission. A study analyzing gene expression in the rat frontal cortex found that Selank administration resulted in significant changes in the expression of 45 genes related to neurotransmission within one hour. Specifically, it influenced the expression of GABA receptor subunits, ion channels, and transporters, suggesting a complex regulatory role rather than simple receptor binding[4]. This modulation allows for anxiolytic effects without the broad suppression of CNS activity that causes sedation.
¶ 2. Upregulation of BDNF
One of the most significant longevity-related mechanisms of Selank is its ability to rapidly increase the levels of Brain-Derived Neurotrophic Factor (BDNF). Studies have demonstrated that intranasal administration of Selank increases BDNF expression in the hippocampus, a brain region critical for memory and emotional regulation[5][6]. BDNF is a key protein for neuroplasticity, neuronal survival, and the maintenance of cognitive function during aging.
¶ 3. Modulation of Monoamine Neurotransmitters
Selank affects the metabolism of monoamine neurotransmitters, including serotonin, dopamine, and norepinephrine. By stabilizing the levels of these neurotransmitters and their metabolites (such as 5-HIAA and DOPAC) in the brain, Selank contributes to mood stabilization and cognitive alertness[7].
¶ 4. Inhibition of Enkephalin Degradation
The Pro-Gly-Pro sequence in Selank makes it resistant to enzymatic degradation. Furthermore, Selank has been shown to inhibit the enzymes responsible for breaking down endogenous enkephalins (natural opioids), thereby prolonging their half-life. This action may contribute to its stress-protective and pain-modulating effects[1:1].
¶ 5. Immunomodulation
As an analog of tuftsin, a peptide integral to immune function, Selank retains immunomodulatory capabilities. It has been observed to influence the expression of cytokines (such as IL-6) and modulate the balance of T-helper cells (Th1/Th2), potentially supporting immune system resilience under stress[8].
¶ Evidence and Research Status
Most clinical research on Selank has been conducted in Russia, where it is an approved pharmaceutical. Western research is primarily limited to preclinical animal studies, though the mechanism of action has been explored in international journals.
¶ Generalized Anxiety Disorder (GAD) and Neurasthenia
Clinical trials in Russia have evaluated Selank's efficacy in treating Generalized Anxiety Disorder (GAD) and neurasthenia. A comparative study involving 62 patients found that Selank (used as 0.15% nasal drops) was as effective as the benzodiazepine phenazepam in reducing anxiety symptoms. However, unlike phenazepam, Selank improved asthenic symptoms (fatigue, weakness) and cognitive functions such as memory and attention, without causing sedation or withdrawal symptoms[3:1][9].
- GRADE Rating: Low (Based on limited number of trials, primarily non-English/Russian origin, though published in translated journals).
¶ Cognitive Enhancement and Nootropic Effects
In animal models, Selank has consistently demonstrated the ability to improve learning and memory consolidation. It has been shown to restore cognitive function in rats with ethanol-induced memory impairment and in conditions of acute stress[10]. In human subjects with anxiety-asthenic disorders, Selank treatment led to subjective and objective improvements in mental clarity and focus[3:2].
¶ Neuroprotection and Alcohol Withdrawal
Preclinical studies suggest Selank may offer neuroprotective benefits in the context of substance withdrawal. In rat models of chronic alcohol exposure, Selank administration prevented the accumulation of cognitive deficits usually seen during withdrawal, likely mediated through its effects on hippocampal BDNF levels[10:1].
¶ Safety and Side Effects
The safety profile of Selank is considered one of its primary advantages over traditional anxiolytics.
- Sedation: Selank does not induce sedation or muscle relaxation.
- Cognitive Impact: Unlike benzodiazepines, it does not impair reaction time or memory; conversely, it often improves them.
- Dependence: There are no reports of tolerance, physical dependence, or withdrawal symptoms associated with Selank use in clinical studies[3:3].
- Toxicity: The peptide has shown very low toxicity in animal studies. As it breaks down into endogenous amino acids, it does not burden the liver or kidneys significantly.
- Contraindications: Due to lack of data, it is generally advised to avoid use during pregnancy and breastfeeding.
¶ Practical Notes
¶ Administration
Selank is typically administered intranasally (nose drops or spray). This route allows the peptide to bypass the blood-brain barrier more effectively and enter the CNS directly via the olfactory and trigeminal nerve pathways.
- Standard Concentration: 0.15% solution.
- Typical Protocol: 2-3 drops in each nostril, 2-3 times per day, for courses of 10-14 days.
¶ Availability
- Russia: Approved as a prescription drug (brand name "Selank") for the treatment of anxiety and neurasthenia.
- United States/Europe: Not FDA or EMA approved. It is available as a research peptide or through compounding pharmacies, but remains unregulated for human use in these regions.
¶ Storage
As a peptide, Selank solution can be fragile. It is typically recommended to keep it refrigerated (2-8°C) to maintain potency, especially after opening.
¶ References
Ashmarin IP, et al. [Pro-gly-pro-peptide derivatives of tuftsin: new anxiolytic drugs]. Vestn Ross Akad Med Nauk. 2004;(5):36-40. ↩︎ ↩︎
Zozulya AA, 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):315-7. ↩︎
Zozulya AA, 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. ↩︎ ↩︎ ↩︎ ↩︎
Volkova A, et al. Selank Administration Affects the Expression of Some Genes Involved in GABAergic Neurotransmission. Front Pharmacol. 2016;7:31. ↩︎
Inozemtseva LS, et al. Intranasal administration of the peptide Selank regulates BDNF expression in the rat hippocampus in vivo. Dokl Biol Sci. 2008;421:238-40. ↩︎
Semenova TP, et al. Effect of selank on the content of brain-derived neurotrophic factor in the hippocampus of rats with different phenotypes of the nervous system. Bull Exp Biol Med. 2010;150(1):34-6. ↩︎
Semenova TP, et al. Comparison of the effects of selank and tuftsin on the metabolism of serotonin, dopamine, and norepinephrine in the brain of mice with different phenotypes of emotional and stress reactions. Bull Exp Biol Med. 2010;149(5):602-5. ↩︎
Uchakina ON, et al. [Immunomodulatory effects of selank in patients with anxiety-asthenic disorders]. Zh Nevrol Psikhiatr Im S S Korsakova. 2008;108(5):71-5. ↩︎
Pitsikova N, et al. [Use of the new peptide anxiolytic selank in the therapy of generalized anxiety disorders]. Zh Nevrol Psikhiatr Im S S Korsakova. 2008;108(4):38-48. ↩︎
Sudakov SK, et al. Selank, Peptide Analogue of Tuftsin, Protects Against Ethanol-Induced Memory Impairment by Regulating of BDNF Content in the Hippocampus and Prefrontal Cortex in Rats. Bull Exp Biol Med. 2019;168(2):229-232. ↩︎ ↩︎