In vitro screening of major neurotransmitter systems possibly involved in the mechanism of action of antibodies to S100 protein in released-active form

Abstract

Experimentally and clinically, it was shown that released-active form of antibodies to S100 protein (RAF of Abs to S100) exerts a wide range of pharmacological activities: anxiolytic, antiasthenic, antiaggressive, stress-protective, antihypoxic, antiischemic, neuroprotective, and nootropic. The purpose of this study was to determine the influence of RAF of Abs to S100 on major neurotransmitter systems (serotoninergic, GABAergic, dopaminergic, and on sigma receptors as well) which are possibly involved in its mechanism of pharmacological activity. Radioligand binding assays were used for assessment of the drug influence on ligand–receptor interaction. [35S]GTPγS binding assay, cyclic adenosine monophosphate HTRF™, cellular dielectric spectroscopy assays, and assays based on measurement of intracellular concentration of Ca2+ ions were used for assessment of agonist or antagonist properties of the drug toward receptors. RAF of Abs to S100 increased radioligand binding to 5-HT1F, 5-HT2B, 5-HT2Cedited, 5-HT3, and to D3 receptors by 142.0%, 131.9%, 149.3%, 120.7%, and 126.3%, respectively. Also, the drug significantly inhibited specific binding of radioligands to GABAB1A/B2 receptors by 25.8%, and to both native and recombinant human sigma1 receptors by 75.3% and 40.32%, respectively. In the functional assays, it was shown that the drug exerted antagonism at 5-HT1B, D3, and GABAB1A/B2 receptors inhibiting agonist-induced responses by 23.24%, 32.76%, and 30.2%, respectively. On the contrary, the drug exerted an agonist effect at 5-HT1A receptors enhancing receptor functional activity by 28.0%. The pharmacological profiling of RAF of Abs to S100 among 27 receptor provides evidence for drug-related modification of major neurotransmitter systems.

Dose-dependent antiviral activity of released-active form of antibodies to interferon-gamma against influenza A/California/07/09(H1N1) in murine model

“…A dose–response relationship was confirmed by the statistical difference established for the antiviral activity of AC in comparison to the control group with the AC dose increment. This manner of action corresponds to the in vitro results obtained for this class of drugs [Gavrilova et al, ; Pschenitza et al, ; Gorbunov et al, ]. We also were able to determine the most appropriate dose and the direct correlation between dose of the virus inoculation and the suitable dose of the drug for treatment.…”

The Spatial Homeostasis Hypothesis

“…First of all, we were interested in practical research of the discovered phenomenon, including its molecular mechanisms (for example, [29][30][31][32]). Ultimately, our studies lead to the development of a new group of drugs based on "high dilutions" of antibodies: "released-active" antibodies.…”

The phenomenon of released‐activity. Reply on comment on Don et al.: Dose‐dependent antiviral activity of released‐active form of antibodies to interferon‐gamma against influenza A/California/07/09(H1N1) in murine model

“…More than 100 PhD theses have been defended in our field, more than 75 monographs and more than 1000 scientific articles have been published, including in foreign journals such as PLOS One , Antiviral Research , International Journal of Infectious Diseases , Nutrition & Diabetes , International Journal of Endocrinology , Journal of Pharmacy and Pharmacology , Pharmacology Biochemistry & Behavior , Inflammation , Journal of Diabetes Research , Journal of Sexual Medicine , Sensors (references to some of the articles are presented below) …”