Selank
What is Selank?
Selank is a synthetic heptapeptide derived from the naturally occurring peptide, Tuftsin. Developed in Russia, it has shown promise for its anxiolytic, nootropic, and immunomodulatory effects, positioning it as a potential therapeutic for anxiety disorders and cognitive enhancement.
Structure and Mechanism
- Peptide Sequence: Thr-Lys-Pro-Arg-Pro-Gly-Pro
- Molecular Formula: C33H57N11O9
- Molecular Weight: 751.887 g/mol
Selank works by modulating the GABAergic system, similar to benzodiazepines but without the side effects of dependence or withdrawal. It also influences gene expression related to inflammation, immune function, and cognitive processes.
Key Benefits
- Anxiolytic Effects: Studies have shown that Selank effectively reduces anxiety symptoms, comparable to benzodiazepines but without causing sedation or dependence.
- Cognitive Enhancement: Improves learning and memory, as demonstrated in animal studies where Selank administration led to faster learning and improved memory retention.
- Immune Modulation: Regulates immune responses, including cytokine levels, offering potential therapeutic applications for immune-related conditions.
- Potential for Alcohol Withdrawal Support: Reduces withdrawal symptoms in animal models, suggesting a possible role in addiction recovery.
- Cardiovascular Benefits: Lowers blood pressure and increases cerebral blood flow in animal studies.
Research Highlights
- Anxiety Treatment: Clinical trials with patients with generalized anxiety disorder (GAD) found Selank as effective as standard treatments, with additional cognitive benefits.
- Memory and Learning: Enhances memory trace stability, likely due to modulation of specific genes related to cognitive processes.
- Immune Support: Demonstrates immunomodulatory effects, including regulation of IL-6, indicating benefits for inflammatory and immune conditions.
Suggested Use
- Selank Nasal Spray: 1 spray per nostril daily, increasing to twice daily after the second week.
Storage
- Keep frozen until first use; refrigerate thereafter at 2°C - 8°C for up to 60 days.
How was Selank discovered?
Tuftsin, the natural peptide, was first discovered between 1970 and 1980 at the Tufts University – the place after which the peptide was named (2,3).
After its discovery, it was found that Tuftsin is involved in several functions of the phagocytic cells, including phagocytosis, motility, and immunological cell functions (2).
Since the discovery, several synthetic analogs of Tuftsin have been synthesized in the laboratory by two methods, namely conventional and polymeric reagent methods(4). While the specific details remain uncertain, it is understood that during one such synthetic development, Selank was produced at the Institute of Molecular Genetics of the Russian Academy of Sciences (6).
Complete Guide to Selank peptide
Generalized anxiety disorder (GAD) is characterized by tremendous anxiety and worrisome behavior about day-to-day chores, for no apparent reason. Patients suffering from GAD expect the most negative outcome and tend to remain stressful and ‘edgy’ throughout the day. GAD is not uncommon, and more than 2% of the US population, mainly women, suffer from GAD (1).
There are several anxiolytic medications available to treat anxiety, however, they tend to cause severe side effects, such as drug dependence.
Peptides, on the other hand, are very commonly being used to diagnose and treat such common ailments. Both natural and synthetic peptides are highly stable in the body and tend to cause comparatively lesser side effects, if any.
One such anxiolytic peptide is Selank. Selank has several benefits besides treating anxiety, which include nootropic effects (i.e., boosts mental skills) and immunomodulatory effects (i.e., regulates the immune system).
How does it work?
Selank is composed of two entities – one is a short fragment from the human immunoglobulin G (IgG) and the other is a tripeptide Pro-Gly-Pro at the end of the molecule. These two entities are responsible for the duration of action of the peptide and lead to enhanced peptide stability (6).
Stimulating the GABAergic system
Studies have shown that Selank works through a similar mechanism as that of the benzodiazepines, a class of medications used to treat anxiety, and act on the gamma aminobutyric acid (GABA) receptors.
In this study (7), the expression of 84 genes that are involved in neurotransmission was studied in rats. The experimental rats were administered with either 300 microg per kg Selank or GABA and the gene expression was studied after 1 and 3 hours of administration, using the PCR method.
All the gene expressions that were studied for both Selank and GABA were positively correlated to each other. The results showed that Selank caused several alterations in the neurotransmission process, demonstrating that Selank executes its effects via modulating the GABAergic system.
Genome expression and role in inflammatory process
Studies were conducted to understand the role of Selank peptide on genome expression and thereby its involvement in the inflammatory process.
These studies (8) were carried out on male rats weighing 250 grams. These rats were separated into three groups – one was administered with control, another with a single administration of Selank, and the last group was administered with Selank for 5 days. The dose of Selank administered was 200 micrograms / kg body weight, via the intranasal route. After the study, the RNA was isolated from the rat spleen and hippocampus and studied via PCR method.
Based on the results, it was determined that Selank caused gene expression, more strongly on the spleen and the hippocampus. One of the gene expressions involved was the change in CX3CR1, which is involved in the inflammatory process. This suggested that Selank regulates the inflammatory process through the mechanism of gene expression, mainly the CX3CR1 alteration.
What are the benefits of Selank?
Based on the current available studies, there are several advantages of Selank, including:
- Elevate learning ability and memory
- Improve immune system
- Blood pressure treatment
- Reduce weight
- Decrease cholesterol levels
- Reduce stress
- Potential treatment for alcohol withdrawal
- Treatment of anxiety
Research and Clinical studies
Anxiolytic effects in patients suffering from GAD
In this study (9), 62 patients suffering from Generalized Anxiety Disorder (GAD) were examined.
These patients were divided into 2 groups – 30 patients were treated with Selank, whereas 32 patients were treated with Medazepam. Medazepam is an anxiolytic medication, belonging to the group of benzodiazepines.
After the study, the psychometric levels of all patients were analyzed. Results demonstrated that the effects of Selank were the same as that of Medazepam, with additional positive psychostimulant effects.
Enkephalin levels of tau leu-enkephalin had significantly reduced in the Selank treated patients. This enkephalin is directly related to the duration and severity of GAD. Hence, the reduced levels of enkephalins and positive effects of Selank demonstrated the therapeutic use in the treatment of GAD.
Anxiolytic effects in patients with anxiety and phobia
This study (10) was conducted on 60 patients suffering from anxiety and phobia. A randomized trial was conducted on these patients who were either treated with Selank peptide or Phenazepam, another anxiolytic medication belonging to the class of benzodiazepines.
The result of this study demonstrated significantly positive anxiolytic and nootropic effects of Selank. These effects of Selank lasted for over a week after the last peptide administration. This study further supported the use of Selank in the therapeutic field as an anxiolytic medication.
Memory enhancing effects
This study (11) was conducted on rats that were enrolled in a “training” session of four days for learning conditioned avoidance response (CAR). CAR is a learned response for delaying or preventing the avoidance behavior.
Selank peptide was administered in the rats at a dose of 300 micrograms / kg given 15 minutes before the training session on all four days. Upon monitoring the behavior of the rats, the learning abilities of the rats improved with each given dose as the number of errors reduced, and the number of correct solutions increased.
This study demonstrated that Selank improved the cognitive functioning of the rats and hence can potentially be used as a therapeutic, nootropic agent.
Immunomodulatory effects
This study (12) was conducted on patients suffering from GAD and neurasthenia, who received Selank peptide for 14 days.
After the study, the peripheral blood samples were collected and analyzed. The analytical results showed peak elevation in the levels of IL-6 cytokine and changes in the Th1 and Th2 cytokine ratio, all of which regulate the immune system in the body.
These results demonstrated that Selank possesses immunomodulatory properties and can potentially be used to regulate the human immune system.
Controlling alcohol withdrawal symptoms
In this study (13), rats were infused with 10% ethanol as their sole source of fluid for 24 weeks. Consequently, these rats were experimentally induced with alcohol withdrawal symptoms, once the ethanol administration was stopped.
A single dose of 0.3mg / kg body weight of Selank was administered in these rats via intraperitoneal route.
After 48 hours of administration, it was seen that the alcohol withdrawal symptoms had drastically reduced, based on the results of their social interaction and maze tests. These results suggest that Selank can potentially be used to treat alcohol withdrawal symptoms in humans, once clinically tested.
Cardiovascular effects
In this study (14), Selank was administered at a given dose of 300 mg / kg via an intravenous route in cats. The main goal of this study was to examine the cardiovascular and respiratory effects of the peptide in animals.
Upon administration, it was noticed that there was a 32% decrease in the arterial blood pressure within 3 minutes of injection. What’s more, the peptide also caused a 24% increase in the cerebral blood flow within the first 10 minutes of administration, which then slowly decreased up to its optimal levels. Selank did not induce any effects on the respiratory system or the heart rate.
This study demonstrated that Selank may potentially be used for controlling blood pressure in humans once clinically tested.
Weight loss and cholesterol reduction
In this study (15), 37 rats were first exposed to a high fat diet for 6 consecutive weeks, until the weights of rats were up to 280 to 300 grams. Later, these rats were divided into two groups, where the control group that was treated with 0.85% sodium chloride and the experiment group that was treated with 75 micrograms / kg body weight of Selank peptide, both administered via intranasal route. Also, a group of normal, healthy rats were used for this study that were not administered with either of the agents but were simply monitored for the purpose of this study.
Upon analysis, it was determined that the Selank treated group showed decreased levels of cholesterol and fat by up to 25% to 58%. The fat metabolism rate of the Selank treated group also improved and was eventually the same rate as that in the normal, healthy rats.
Upon weight determination of the rats, it was noted that the control group showed an average weight gain of 40g throughout the study, whereas the experiment group maintained the same weight throughout the study, with gradual weight reduction upon peptide administration.
Selank side effects
Selank and benzodiazepines
Given that the studies(7,9,10) have shown that Selank demonstrates similar mechanisms and effects as that of benzodiazepines, one of the first questions that arises is whether Selank also causes similar side effects? The answer is no.
Clinical research (7) has demonstrated that Selank does not cause any amnesia, drug dependence or withdrawal symptoms, which are otherwise common with other anxiolytic drugs.
Other side effects
Considering that the peptide is similar to the endogenous peptide (Tuftsin) and is highly stable(6), there may be limited side effects of Selank. However, currently there is very limited data available to confirm any additional side effects of Selank and clinical studies are still ongoing.
Some common side effects, as seen with all peptides, may include:
- Poor oral bioavailability (16)
- Pain and irritation at the site of injection (if administered via injection)
- Dizziness, headache, and nausea
Peptide profile
Pharmacokinetic studies
In order to determine the distribution rate and pharmacokinetics profile of Selank, several in vitro and in vivo experiments were conducted on rats.
Studies (17) have shown that the heptapeptide Selank is detected in the blood plasma only for up to 10 minutes, suggesting that the peptide gets eliminated (or metabolized) within 10 minutes of administration. What’s more, the peptide was well distributed in the vascularized organs, more in the liver, followed by kidneys and then the heart.
Intranasal vs. Intraperitoneal routes of administration
In order to determine the pharmacological effects of the peptide based on their routes of administration, a research study (18) was conducted on inbred mice who were administered with 300 micrograms / kg body weight of daily dose of Selank for 5 days via both intraperitoneal and intranasal routes. The binding rate of the blood markers to the NMDA and GABA brain receptors was measured.
After the study, it was determined that the binding sites increased by 38% in the mice treated with the intraperitoneal route, whereas it increased by 23% in the mice treated via intranasal route. The differences in the pharmacological effects were attributed to the specific features of the peptide, pertaining to its biotransformation and dynamics of the anxiolytic and nootropic effects. However, clinical studies are still ongoing to determine whether these differences also pertain in humans.
Is Selank approved by the US FDA?
While there is sufficient data online to suggest the Selank is clinically approved in Russia and is included in the Russian List of Essential Medicines and Health Products Information Portal, it must be noted that Selank is not clinically approved by the US FDA.
Even so, Selank is available in several online platforms, mainly from Russia and Ukraine, and is available for research purposes only.
Summary
Selank is a potent synthetic heptapeptide analogous to the endogenous peptide called Tuftsin.
Selank mainly exerts its effects via acting on the GABAergic system and modulating gene expressions. Consequently, Selank has demonstrated promising effects in the treatment of anxiety, as an anxiolytic agent, and in enhancing the cognitive responses, as a nootropic agent.
Several research studies have shown that Selank possesses additional positive effects as well, however, clinical studies are yet to be conducted and clinical results on human volunteers are awaited.
Currently, Selank is an approved medication in Russia and Ukraine and is yet to be approved by the FDA. While studies are ongoing to obtain this approval, Selank is available online and can be purchased in small quantities for the sole purpose of research from approved suppliers.
Selank is a short, synthetic analogue of tuftsin. It has profound anti-anxiety properties. Selank also boosts memory and learning and has been shown to have beneficial effects on pain perception.
Selank Overview
Selank, which was developed in Russia, is a short peptide with nootropic and anxiolytic properties. It is a synthetic analogue of naturally occurring Tuftsin, an immunomodulatory peptide that modulates IL-6, T helper cells, monoamine neurotransmitters, and brain-derived neurotropic factor (BDNF). In fact, Selank and Tuftsin are essentially the same except that Selank has an additional four amino acids in its chain that help to improve metabolic stability and half-life. Selank has been tested in clinical trials as a potential treatment for generalized anxiety disorder.
Selank Structure:
Sequence: Thr-Lys-Pro-Arg-Pro-Gly-Pro
Molecular Formula: C33H57N11O9
Molecular Weight: 751.887 g/mol
PubChem CID: 11765600
CAS Number: 129954-34-3
Synonyms: Selanc
Referenced Citations
[1] A. Volkova et al., “Selank Administration Affects the Expression of Some Genes Involved in GABAergic Neurotransmission,” Front. Pharmacol., vol. 7, Feb. 2016. [PubMed]
[2] A. Kasian et al., “Peptide Selank Enhances the Effect of Diazepam in Reducing Anxiety in Unpredictable Chronic Mild Stress Conditions in Rats,” Behavioural Neurology, 2017. [Online]. Available: https://www.hindawi.com/journals/bn/2017/5091027/.
[3] A. A. Zozulya et al., “The inhibitory effect of Selank on enkephalin-degrading enzymes as a possible mechanism of its anxiolytic activity,” Bull. Exp. Biol. Med., vol. 131, no. 4, pp. 315–317, Apr. 2001. [PubMed]
[4] O. Y. Sokolov, V. K. Meshavkin, N. V. Kost, and A. A. Zozulya, “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. [PubMed]
[5] O. N. Uchakina et al., “[Immunomodulatory effects of selank in patients with anxiety-asthenic disorders],” Zh. Nevrol. Psikhiatr. Im. S. S. Korsakova, vol. 108, no. 5, pp. 71–75, 2008. [PubMed]
[6] A. A. Zozulia 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, vol. 108, no. 4, pp. 38–48, 2008. [PubMed]
[7] T. Kolomin, M. Shadrina, L. Andreeva, P. Slominsky, S. Limborska, and N. Myasoedov, “Expression of inflammationrelated genes in mouse spleen under tuftsin analog Selank,” Regul. Pept., vol. 170, no. 1–3, pp. 18–23, Oct. 2011. [PubMed]
[8] T. I. Agapova et al., “[Effect of semax on the temporary dynamics of brain-derived neurotrophic factor and nerve growth factor gene expression in the rat hippocampus and frontal cortex],” Mol. Genet. Mikrobiol. Virusol., no. 3, pp. 28– 32, 2008. [PubMed]
[9] T. P. Semenova, I. I. KozlovskiÄ, N. M. Zakharova, and M. M. Kozlovskaia, “[Experimental optimisation of learning and memory processes by selank],” Eksp. Klin. Farmakol., vol. 73, no. 8, pp. 2–5, Aug. 2010. [PubMed]
[10] T. A. Kolomin et al., “[c],” Zh. Vyssh. Nerv. Deiat. Im. I. P. Pavlova, vol. 63, no. 3, pp. 365–374, Jun. 2013.
[11] T. P. Semenova, M. M. Kozlovskaya, N. M. Zakharova, I. I. Kozlovskii, and A. V. Zuikov, “Effect of selank on cognitive processes after damage inflicted to the cerebral catecholamine system during early ontogeny,” Bull. Exp. Biol. Med., vol. 144, no. [PubMed]
[12] N. V. Kost et al., “[Semax and selank inhibit the enkephalin-degrading enzymes from human serum]],” Bioorg. Khim., vol. 27, no. 3, pp. 180–183, Jun. 2001. [Springer]