Publications in Scientific Journals

The results and findings of studies of preclinical and clinical efficacy and safety of the Company’s medications and their components are published in Russian and international peer-reviewed scientific journals, including those indexed by international bibliographic databases.

List of publications

Complex therapy of anxiety states in patients with somatic profile

There is a close relationship between the development of anxious, depressive and other neurotic disorders and brain specific S-100 protein. Tenoten composition includes a release-active antibodies to brain specific S-100 protein (R-AA S-100). The efficiency of destination Tenoten in complex therapy of anxiety disorders in patients of somatic profile in the dose of 1-2 tablets 3 times a day, 4 weeks therapy course. The initial decrease in anxiety level observed after 2 weeks of therapy. Tenoten antianxiety effect is not inferior such anxiolytic as tofisopam and antidepressants as clonazepam and phenazepamum.

Antibodies to calcium-binding S100B protein block the conditioning of long-term sensitization in the terrestrial snail

The effects of antibodies to calcium-binding S100B protein diluted to 10(-12) (LAS100B) on the long-term sensitization in the Helix lucorum snail (neurobiological model of the anxious-depressive state) were evaluated. The administration of LAS100B prior to conditioning of long-term sensitization in the terrestrial snail 10 min prior to the first electric stimulus) prevents strengthening of the defensive reaction of withdrawing the ommatophores (eye tentacles) and the defensive reaction of closing the pneumostome. This effect is termed "protective", as it prevents the conditioning of long-term sensitization. At the same time, snails given an injection of saline developed long-term sensitization with a significant strengthening of the defensive reactions of withdrawing the ommatophores and closing the pneumostome. When LAS100B was administered before long-term sensitization in advance, the membrane and threshold potentials of premotor interneurons, which regulate defensive behaviour, decreased to a significantly lesser extent compared to the long-term sensitization arm. It is possible that the "protective" effect is linked to the mechanisms of maintaining the membrane potential and changes in extra- and intracellular balance of calcium-binding S100B protein.

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

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.

Investigation of changes in NO content during long-term sensitization in edible snail using EPR-spectroscopy: effects of antibodies to calcium-binding protein S-100

EPR-spectroscopy experiments (electron paramagnetic resonance) demonstrated a decrease in NO production in the nervous system and heart of edible snail Helix lucorum after formation of long-term sensitization, a neurobiological model of anxiety and depression. The protective effect of antibodies to Ca(2+)-binding protein S-100 in dilution of 10(-12) on the formation of long-term sensitization was accompanied by partial recovery of NO synthesis in the nervous system and heart. These findings indicate that the imbalance in Ca(2+)-binding protein S-100 can lead to inhibition or modulation of some processes during plastic reorganization in the body and especially during pathological processes.

Anxiolytic activity of tenoten and diazepam depends on conditions in Vogel conflict test

We compared two modifications of Vogel conflict test and assessed anxyolitic activity of two drugs: diazepam (benzodiazepine anxiolitic) and tenoten (ultra-low doses of antibodies to S-100 protein) in both modifications of the test. It was found that the intensity of anxiolitic effect of the drugs depends on the conditions of Vogel test.

Release-active antibodies to S100 protein are able to improve the experimental allergic encephalomyelitis

AIM: To reveal the effects of release-active antibodies to S100 protein in an animal model of multiple sclerosis.
MATERIAL AND METHODS: Sixty female Wistar rats, aged 12 weeks, were included in the study. The pathology was induced by subcutaneous injection of the spinal cord homogenate. Afterwards the rats received a water solution of release-active antibodies to S100 protein (2,5 ml/kg/day, tenoten) or distilled water intragastrically during 30 days. Intramuscular injections of glatiramer acetate (4 mg/kg/day, copaxone) were used as a positive control.
RESULTS AND CONCLUSION: Release-active antibodies to S100 protein enhanced the latency period of the disease, reduced its peak intensity and compensated the loss of body weight of the animals. The experimental drug effect was similar to the results of copaxone injections.

Antibodies to S100 proteins have anxiolytic-like activity at ultra-low doses in the adult rat

S100 proteins are small calcium-binding proteins interacting with numerous intra- and extra cellular targets involved in diverse physiological functions. In particular, S100 proteins may be involved in the regulation of anxiety-related behaviour. In the present study, the effects of affinity-purified antibodies to S100 proteins administered orally at ultra-low doses were evaluated in pre-clinical tests for anxiolytic-like activity in the adult rat. In the Vogel conflict test in the rat, antibodies to S100 proteins increased punished drinking (anti-conflict effect) at 5 and 7.5 mL kg(-1), but not at 2.5 or 10 mL kg(-1). Antibodies to S100 proteins increased the percentage of entries into the open arms of an elevated plus-maze at 10 mL kg(-1), but not at lower doses. Taken together, these results indicate the presence of anxiolytic-like activity for antibodies to S100 proteins over the dose range 5-10 mL kg(-1) in the adult rat.

Farmacological effects of anti-S 100 in release-active form and mechanisms of their realization

Antibodies to 5100 proteins (anti-5100) in release-active form (RA anti-5100) are an active component of some domestic drugs(tenoten, tenoten for children, divaza, brizantin, kolofort and proproten-100). The authors present the results of preclinical and clinical trials (with detailed consideration of experimental data) which demonstrated a wide spectrum of specific pharmacological activity and safety as well as mechanisms of anti-5100 action.