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

Current possibilities in pharmacotherapy of anxiety disorders in children and adolescents

Objective  to assess the efficacy and safety of tenoten for kids in the treatment of children and adolescents with anxiety disorders. Material and methods. It was conducted a multicenter, double-blind, placebo-controlled trial of the drug tenoten for kids at a dose of 1 tablet 3 times a day for 12 weeks. The study included 98 patients (boys and girls from 5 to 15 years with a confirmed diagnosis of anxiety disorder), randomized into two groups: the first included 48 patients treated tenoten for kids, in the second — 50 patients receiving placebo. 
Results and conclusion. Tenoten for kids has a strong anti-anxiety effect both on the results of self-assessment of patients, and on the reports of parents. This anxiolytic activity of the drug manifested most significantly in children aged 5 to 7 years. In addition, in patients 8—15 years of treatment spent tenoten for kids to regress the symptoms of anxiety disorders by anxiety subscales SCAS «Separation anxiety», «panic attacks and agoraphobia» and «social phobia». Throughout the course of treatment tenoten for kids have been no adverse events. 

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.

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.

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.