Peptide-based Anxiolytics: The Molecular Aspects of Heptapeptide Selank Biological Activity.
Vyunova. Tatiana V TV; Andreeva. Lioudmila L; Shevchenko. Konstantin K; Myasoedov. Nikolay N
Key Findings
- Selank acts as a positive allosteric modulator of GABA receptors, enhancing GABA binding.
- When combined with benzodiazepines, Selank changes GABA binding in a non‑additive way and can block the modulatory effects of diazepam and olanzapine.
- The peptide’s effect appears to be concentration‑dependent and may target specific GABA receptor subtypes.
Practical Outcomes
- For self‑experimenters, Selank could be considered as an alternative or adjunct anxiolytic that may avoid some side effects of traditional benzodiazepines. However, because the data are limited to molecular studies, start with low doses and avoid mixing it with prescription anti‑anxiety meds until more human safety and efficacy data are available.
Summary
Selank is a tiny protein that can calm anxiety by tweaking the brain's GABA system, similar to how some anti‑anxiety drugs work. It boosts GABA activity in a way that depends on the dose and can change how drugs like diazepam act, sometimes blocking their effects. This suggests Selank might be useful on its own or in combination with other anxiolytics, but the evidence is still early‑stage and mostly from lab experiments.
Abstract
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. In this issue, we tried to find the molecular mechanisms which may underlie Selank antianxiety effects. 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. 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. 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.
Study Information
pubmed
2018
2018-11-30T00:00:00.000Z
10.2174/0929866525666180925144642
9