Selank

Selank is a synthetic heptapeptide developed by combining the naturally occurring immunomodulatory tetrapeptide tuftsin (Thr-Lys-Pro-Arg) with a stabilising Pro-Gly-Pro C-terminal extension derived from proline-rich peptides. This modification significantly increases metabolic stability and plasma half-life compared to native tuftsin, which is rapidly degraded by aminopeptidases.

At the molecular level, Selank modulates the expression of brain-derived neurotrophic factor (BDNF) and its receptor TrkB in the hippocampus and prefrontal cortex, regions critical for memory consolidation and emotional regulation. It also influences the balance of monoamine neurotransmitters, increasing serotonin metabolism in the brain and modulating the enkephalin-degrading enzymes, thereby indirectly enhancing endogenous opioid peptide activity without direct opioid receptor binding.

Selank has been shown to influence the expression of approximately 50 genes related to GABAergic neurotransmission, inflammatory cytokine production, and neurotrophic signalling. It inhibits the expression of pro-inflammatory cytokines IL-6 and TNF-alpha while upregulating anti-inflammatory IL-10, contributing to its combined anxiolytic and immunomodulatory profile. Unlike benzodiazepines, Selank does not produce sedation, tolerance, or dependence in preclinical models.

Selank was developed in the late 1990s at the Institute of Molecular Genetics of the Russian Academy of Sciences, under the direction of Nikolai Myasoedov. The design rationale was to create a metabolically stable analogue of tuftsin that retained immunomodulatory properties while also exhibiting central nervous system activity.

Early research demonstrated that Selank possessed anxiolytic properties comparable to benzodiazepines in animal models without the characteristic sedation, cognitive impairment, or dependence liability. It was approved as a nasal spray medication in Russia in 2009 for the treatment of generalised anxiety disorder and neurasthenia. Subsequent research expanded into cognitive enhancement, revealing that Selank improves memory trace stability, attentional processing, and learning in both animal and human studies. Its dual immunomodulatory and neuroprotective profile has also made it a subject of research in neuroimmunology and stress-related disorders.