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Selank: Preclinical research on anxiety, cognition, and BDNF

Selank: Preclinical research on anxiety, cognition, and BDNF
Selank is a synthetic heptapeptide with the sequence Thr-Lys-Pro-Arg-Pro-Gly-Pro (TKPRPGP), developed in the 1990s at the Russian Institute of Molecular Genetics as a stable version of the natural immunopeptide tuftsin. In preclinical rodent studies it has shown anxiolytic effects comparable to low-dose benzodiazepines, but without the typical sedation or signs of dependence.

Structure and tuftsin origin

Selank is a linear heptapeptide with no modifications or conjugates. Its first four amino acids (Thr-Lys-Pro-Arg) are identical to tuftsin, a natural immunomodulatory tetrapeptide derived from IgG and produced by leukocytes. The C-terminal Pro-Gly-Pro was added to improve proteolytic stability, since tuftsin itself is degraded in the bloodstream within minutes. The molecular weight is 751.9 Da. Because of this small size, in preclinical models Selank distributes rapidly into brain tissue after systemic administration, and shows particularly good CNS penetration with intranasal delivery in animal studies.

Mechanisms in preclinical models

In preclinical studies Selank acts as a multimodal neuromodulator without a single receptor target. The main proposed mechanism is allosteric modulation of GABA-A receptors: gene expression studies in rat brain show that Selank and GABA produce highly correlated changes in expression of GABA-related genes, suggesting a shared molecular basis. In parallel, it increases BDNF (brain-derived neurotrophic factor) expression in the hippocampus and prefrontal cortex, a key signal for synaptic plasticity and learning. It also affects serotonin, dopamine, and noradrenaline metabolism, and inhibits enkephalin-degrading enzymes, which may contribute to the anxiolytic effect.

Preclinical anxiety studies

In the elevated plus maze test in rats, Selank reduces anxiety-related behavior without affecting locomotor activity, which separates it from classical benzodiazepines that cause sedation. In the study by Kasian et al. (2017) on rats under unpredictable chronic mild stress, the combination of Selank and diazepam was the most effective at normalizing anxiety indicators, suggesting that Selank can modulate GABA-A receptor function in a way that potentiates benzodiazepines. In early Russian clinical studies in patients with generalized anxiety disorder, the effect of Selank was comparable to low-dose medazepam, but without development of dependence or withdrawal syndrome during the observation periods.

BDNF, learning, and neuroplasticity

The most studied neuroplastic mechanism of Selank in preclinical models is its effect on BDNF. In the study by Kolik et al. (2019), Selank at a daily dose of 0.3 mg/kg prevented memory and attention disturbances in rats with chronic ethanol exposure during withdrawal, while normalizing BDNF content in the hippocampus and prefrontal cortex. In active avoidance and reward-based learning tasks, Selank improved performance, particularly in animals with initially poor learning. The authors link these effects to activation of the BDNF/TrkB signaling pathway, which regulates synaptic plasticity and long-term potentiation.

Research peptide status

Selank is not approved for medical use by the FDA, EMA, or any other regulatory body, and remains a research peptide (RUO). Most clinical data come from Russian studies and international publications that have not progressed to regulatory approval. The long-term safety profile in humans outside the studied periods is unknown. Peptid.si supplies Selank with laboratory-verified purity of ≥99% via independent HPLC and MS analysis. The Certificate of Analysis is publicly available in the COA Vault.

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Research Use Only (RUO) This article is intended for educational purposes only. The peptides described are not approved for medical, nutritional, or veterinary use in humans or animals.

References / Links

  1. Volkova A, Shadrina M, Kolomin T, Andreeva L, et al. (2016). Selank Administration Affects the Expression of Some Genes Involved in GABAergic Neurotransmission. Front Pharmacol. Frontiers
  2. Kasian A, Kolomin T, Andreeva L, Bondarenko E, et al. (2017). Peptide Selank Enhances the Effect of Diazepam in Reducing Anxiety in Unpredictable Chronic Mild Stress Conditions in Rats. Behav Neurol. Wiley
  3. Kolik LG, Nadorova AV, Antipova TA, Kruglov SV, et al. (2019). 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. SpringerLink
  4. Filatova E, Kasian A, Kolomin T, Andreeva L, et al. (2017). GABA, Selank, and Olanzapine Affect the Expression of Genes Involved in GABAergic Neurotransmission in IMR-32 Cells. Front Pharmacol. Frontiers
  5. Konstantinopolsky MA, Chernyakova IV, Kolik LG (2022). Selank, a Peptide Analog of Tuftsin, Attenuates Aversive Signs of Morphine Withdrawal in Rats. Bull Exp Biol Med. SpringerLink
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