Peptide-based Anxiolytics: The Molecular Aspects of Heptapeptide Selank Biological Activity

Background: Anxiety and mood disorders are the most abundant mental health problems worldwide. The commonly used in clinical practice anxiolytics are focused on pharmacological modulation of brain GABA receptor system activity. As a rule, their use presents a wide spectrum of clinical issues such as dependence, memory impairment and etc. There is an increasing appreciation of the role of neuropeptides and bioactive lipids in the pathophysiology of mood and anxiety disorders as “mild” agents. Heptapeptide Selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro) exhibits prolonged anti-anxiety and nootropic effects. Objective: In this issue, we tried to find the molecular mechanisms which may underlie Selank antianxiety effects. Methods: The main method we used was the radioligand – receptor method of analysis. We also used HPLC (to obtain and ensure reagents and Selank purity) and the methods of brain cells plasmatic membranes isolation and following detection of protein concentration in membrane samples. Results: It was shown that Selank affect the [3H]GABA binding as a positive allosteric modulator. The joint action of Selank and some of benzodiazepines also regulates activity of [3H]GABA binding in specific manner, which is not cumulative and differs from either substance individually. Selank is able to block the modulatory activity of Diazepam and Olanzapine, the location of their and peptide binding sites apparently not the same, but potentially may partially overlaps. Conclusion: Thus, we hypothesized and showed that one of Selank anti-anxiety molecular mechanisms can be associated with subtype selective concentration - dependent allosteric modulation of GABA receptors.