Selank Half-Life: How Long It Stays Active

Selank Half-Life: How Long It Stays Active

Cognitive & Nootropic Research

No peer-reviewed paper we could find states a single plasma half-life figure for Selank in humans or animals. What the published work does show is how it breaks down: in blood plasma, tritium-labelled Selank was cut into four main fragments, TKPRP, TKP, RP and GP, and in rats the intranasal route was the most effective way of delivering it to the brain (Zolotarev et al., Bioorg Khim, 2006; Ashmarin et al., Bioorg Khim, 2008). This page sets out that breakdown research, the human finding that Selank lengthens the half-life of the body’s own enkephalins, and how half-life in the body differs from how long a Selank Nasal Spray or vial keeps.

Findings

  • Selank is Thr-Lys-Pro-Arg-Pro-Gly-Pro, the four amino acids of tuftsin with a Pro-Gly-Pro tail added, a motif its developers credit with the stability of this peptide family (Shevchenko et al., 2019).
  • In plasma, the major breakdown products were TKPRP, TKP, RP and GP, measured with evenly tritium-labelled peptide (Zolotarev et al., 2006).
  • Compared across intraperitoneal, intranasal, intragastric and intravenous routes in rats, intranasal delivery was optimal for getting Selank into the central nervous system (Ashmarin et al., 2008).
  • Selank inhibited the enzymes that break down enkephalins in human serum and plasma (IC50 15-20 µM), and enkephalin half-life rose during Selank courses in patients with generalised anxiety (2001, 2008).
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What does half-life mean?

A half-life is the time it takes for the concentration of a compound in the blood to fall by half. After one half-life, 50% remains; after two, 25%; after five, about 3%. For peptides, the number depends heavily on route and species: a figure from rat plasma is not a human figure, and an intravenous figure is not an intranasal one. It also describes the parent molecule only. A peptide that is quickly cut into fragments can still act through those fragments, or through effects that outlast it, which is a recurring theme in the Selank literature.

What does the research show about how Selank breaks down?

The tritium-labelling work

The most detailed data come from the Institute of Molecular Genetics in Moscow, where Selank was developed. The group made Selank evenly labelled with tritium across every amino acid, so that every fragment produced by enzymes could be tracked at once. In blood plasma, the pentapeptide TKPRP, the tripeptide TKP and the dipeptides RP and GP were the major products of Selank breakdown. The same study measured Selank in brain tissue after intranasal administration (Zolotarev et al., Bioorg Khim, 2006). The abstract reports the pathway rather than a single half-life number, which is why we do not quote one. Figures circulating online without a primary source are not used here.

Why the Pro-Gly-Pro tail matters

Tuftsin, Selank’s parent, is a four-amino-acid immune peptide (Siebert et al., Curr Med Chem, 2017). Selank adds Pro-Gly-Pro, a glyproline, to its end. A 2019 review from the developing institute attributes the high stability of this family of peptide drugs to the Pro-Gly-Pro sequence, and reports that intranasal administration is a promising way to deliver biologically active peptides to the brain (Shevchenko et al., Biomed Khim, 2019). Earlier work showed simple glyprolines were considerably more stable than Semax against an aminopeptidase and the enzymes of nasal mucus, brain membranes and rat blood (Shevchenko et al., Bioorg Khim, 2013).

What did the research show about the nasal route?

The intranasal route is central to Selank research. When the Moscow group compared four routes in rats using labelled peptide, intranasal administration of both Selank and Pro-Gly-Pro was optimal for delivering the peptides to the central nervous system (Ashmarin et al., Bioorg Khim, 2008). Intranasal Selank also changed expression of BDNF, a growth factor tied to learning and memory, in the rat hippocampus (Inozemtseva et al., Dokl Biol Sci, 2008).

A 2016 mouse study compared intranasal and intraperitoneal Selank. Both routes produced anxiolytic and nootropic effects in BALB/c mice, a strain with higher baseline anxiety. The intranasal route raised NMDA receptor binding sites in the hippocampus by 23%, while the intraperitoneal route raised GABA receptor binding in the frontal cortex by 38%, which the authors linked to differences in how each route delivers and processes the peptide (Vasil’eva et al., Eksp Klin Farmakol, 2016). The two routes are compared further in Semax and Selank: intranasal vs subcutaneous research routes.

Selank and the half-life of enkephalins

The human half-life data in Selank research concern a different molecule. Enkephalins are the body’s own opioid-like peptides, and the enzymes that degrade them decide how long they last. Selank inhibited enkephalin-degrading enzymes in human serum with an IC50 (the concentration that blocks half the activity) of 20 µM, stronger than the reference inhibitors puromycin and bacitracin (Kost et al., Bioorg Khim, 2001), and inhibited the breakdown of plasma enkephalin with an IC50 of 15 µM (Zozulya et al., Bull Exp Biol Med, 2001).

That 2001 study found enkephalin half-life was markedly shortened in patients with generalised anxiety. In the 2008 clinical study of 62 patients with generalised anxiety disorder or neurasthenia, serum enkephalin half-life correlated with symptom severity and rose during the Selank course, mostly in the generalised anxiety group (Zozulia et al., Zh Nevrol Psikhiatr Im S S Korsakova, 2008). The clinical results are covered in Selank and anxiety: the research.

How does Selank compare with related peptides?

PeptideBuilt fromPublished breakdown findings
SelankTuftsin plus Pro-Gly-ProTKPRP, TKP, RP, GP in plasma
SemaxAn ACTH fragment plus Pro-Gly-ProHFPGP and PGP with nerve cells
Simple glyprolinesPro-Gly-Pro familyMore stable than Semax to peptidases

Semax findings are from the same 2006 tritium study (Zolotarev et al.); the glyproline comparison is from 2013 (Shevchenko et al.). Semax is covered in Semax half-life and the pair in Semax vs Selank.

What does this mean for study design?

Because Selank is cut into fragments in plasma, studies that track it need an assay that tells the parent peptide from TKPRP, TKP and the dipeptides, as the evenly labelled method did. Route also shapes the readout: intranasal and intraperitoneal Selank changed different receptor systems in the 2016 mouse study. And because Selank acts partly by slowing enkephalin breakdown, enkephalin half-life itself has served as a measurable endpoint in human research.

Half-life in the body vs how long a vial or spray keeps

Half-life describes what happens after a peptide enters a living system. Shelf life is a separate question about the product: how long a lyophilised (freeze-dried) vial keeps before mixing, how long it keeps once reconstituted, and how long a ready-mixed nasal spray keeps once opened. Those answers depend on temperature, light and handling, and are set out in How long does Selank last? and How to store a peptide nasal spray. Vials are reconstituted with bacteriostatic water (see the Selank reconstitution guide), and certificates for every product are on the lab reports page.

Selank is supplied for laboratory research use only. The studies above were laboratory and clinical research using research or pharmaceutical preparations.

Frequently asked questions

What is the half-life of Selank?

No peer-reviewed paper we could find states a single plasma half-life figure for Selank. Tritium-labelling research showed it is broken down in plasma into four main fragments: TKPRP, TKP, RP and GP.

What did research show about intranasal Selank?

In rats, intranasal administration was the optimal route for delivering Selank to the central nervous system among four routes tested, and intranasal Selank changed BDNF expression in the hippocampus. In mice, both intranasal and intraperitoneal Selank produced anxiolytic and nootropic effects.

Why does Selank contain Pro-Gly-Pro?

Selank adds Pro-Gly-Pro to the four amino acids of tuftsin. Researchers at the developing institute attribute the high stability of this family of peptide drugs to the Pro-Gly-Pro sequence.

What did research show about Selank and enkephalin half-life?

Selank inhibited enkephalin-degrading enzymes in human serum. In a 2008 study of 62 patients, enkephalin half-life was low in generalised anxiety and rose during the Selank course.

Is half-life the same as how long Selank lasts in the vial?

No. Half-life describes the peptide inside a living system. How long a vial or ready-mixed nasal spray keeps depends on storage temperature, light and handling, which the Selank storage guide covers.

Sources: Zolotarev YuA et al. Evenly tritium-labeled peptides and their in vivo and in vitro biodegradation. Bioorg Khim. 2006. PMID 16637290. Ashmarin IP et al. A comparative analysis of distribution of glyprolines administered by various routes. Bioorg Khim. 2008. PMID 18695718. Shevchenko KV et al. Stability of proline-containing peptides in biological media. Biomed Khim. 2019. PMID 31258142. Shevchenko KV et al. Proteolysis of simple glyprolines by leucine aminopeptidase and enzymes from nasal slime, brain membranes, and rat blood. Bioorg Khim. 2013. PMID 24397030. Siebert A et al. Tuftsin: properties and analogs. Curr Med Chem. 2017. PMID 28745220. Inozemtseva LS et al. Intranasal administration of the peptide Selank regulates BDNF expression in the rat hippocampus in vivo. Dokl Biol Sci. 2008. PMID 18841804. Vasil’eva EV et al. Comparison of pharmacological effects of heptapeptide Selank after intranasal and intraperitoneal administration to BALB/c and C57BL/6 mice. Eksp Klin Farmakol. 2016. PMID 29787664. Kost NV et al. Semax and Selank inhibit the enkephalin-degrading enzymes from human serum. Bioorg Khim. 2001. PMID 11443939. 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. PMID 11550013. Zozulia 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. PMID 18454096.

More on this: What Is Selank? and Selank Benefits: What the Research Shows.

All products supplied by Vistara Labs are intended for laboratory research use only. They are not drugs, are not approved for human or veterinary use, and are not intended to diagnose, treat, cure or prevent any condition. Nothing on this page constitutes medical advice or guidance for use in humans.

References

Selank has been evaluated in small human comparative studies of anxiety-related disorders, not in large multicentre placebo-controlled trials.

  1. [Efficacy and possible mechanisms of action of a new peptide anxiolytic selank in the therapy of generalized anxiety disorders and neurasthenia]Zozulia AA et al. · Zh Nevrol Psikhiatr Im S S Korsakova 2008 · PMID 18454096Comparative clinical study; 30 patients on Selank versus 32 on medazepam.
  2. [A comparison of the anxiolytic effect and tolerability of selank and phenazepam in the treatment of anxiety disorders]Medvedev VE et al. · Zh Nevrol Psikhiatr Im S S Korsakova 2014 · PMID 25176261Comparative clinical study; 60 patients with anxiety or somatoform disorders, Selank versus phenazepam.

Links open the study record on PubMed so the source can be checked directly. Listing a study is not a claim that its findings apply to any other use, product or route of administration. Research use only.

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