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.

Earlier studies have shown that combination of antibodies to S100 protein and to cannabinoid receptor type 1 in released-active form (Brizantin) may possess anxiolytic properties and decrease nicotine dependence. Released-active form of antibodies is a novel approach that permits to modify natural functions of the target molecule (antigen) under investigation. The aim of the present study was to evaluate the anxiolytic-like effect of Brizantin in the light–dark test in mice, according to its ability to influence the number of entries into the lit compartment and the total time spent there. Three doses of Brizantin (2.5, 5, and 10 mL/kg) were compared with diazepam (1 mg/kg), placebo, and vehicle control. Anxiolytic-like effect of the tested drug was shown to be dose dependent, with an increasing trend from 2.5 to 10 mL/kg. Brizantin in its highest dose significantly increased studied behavioral parameters, although its effect was less pronounced than that of the reference drug diazepam (1 mg/kg).

The anxiolytic and antidepressant activities of complex preparations divaza and brizantin containing antibodies to brain-specific protein S100 were estimated using Vogel conflict test and Nomura forced swimming test. Course treatment (5 days) of brizantin in a dose of 2.5 ml/kg and divaza in a dose of 7.5 ml/kg significantly increased punished drinking in the Vogel conflict test in comparison with the control. Both drugs also improved general emotional behavior during training prior to the test procedure. Brizantin and divaza in a dose of 7.5 ml/kg increased the number of wheel revolutions in the Nomura forced swimming test in comparison with the control; the effect of divaza was more pronounced. High correlation coefficients between the number of wheel revolutions during the first and second 5-min sessions are also indicative of antidepressant action of divaza and brizantin.

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Болезнь Альцгеймера (БА) является одним из наибо-лее социально значимых заболеваний, которому, как пра-вило, подвержены лица старшей возрастной группы. При БА отмечается комплексное нарушение структуры и функции мозга: дисфункция базальной холинергической системы, нарушение синаптической пластичности, уменьшение численности нейронов. Дисфункция базаль-ной холинергической системы заключается в том, что в аксонах холинергических нейронов, оказавшихся в зоне *e-mail: tanaevakk@materiamedica.ru накопления растворимых олигомеров бета-амилоида (но-вая кора, гиппокамп, миндалина), развивается затухаю-щая ретроградная нейропатия [1]. Она проявляется нару-шением ремоделирования терминалей аксонов, ослабле-нием синтеза, транспорта и усилением обратного захвата ацетилхолина в нейронах базальной холинергической си-стемы. Нарушение синаптической пластичности в ука-занных зонах приводит к ослаблению долговременной потенциации синаптического проведения и усилению его Цель исследования. Проверка предположения, что препарат диваза, состоящий из релиз-активных антител (РА АТ) к белку S100 и NO-синтетазе (eNOS), может обладать антиамнестическим действием. Материал и методы. Исследование проводили на модели амнезии, вызванной интрацеребровентрикулярной инъекцией фрагмента β-амилоидного пептида 25-35 крысам. Оценивали способность РА АТ к белку S100 (тенотен) и eNOS (импаза) их комбинации -дивазы компенсировать поведенческие отклонения в тестах распознавания новых объектов и условной реакции пассивного избегания. Результаты. Под влиянием РА АТ к S100 наблюдалось восстановление нарушенной кратковременной памяти, РА АТ к eNOS были более эффективны в более позднем периоде (через 24 часа). Комбинированный препарат полностью компенсировал смоделированные нарушения. Кроме того, если тенотен оказывал максимальное влияние на когнитивные функции, то импаза больше действовала на эмоциональную составляющую. Диваза оказывала более эффективное влияние на амнезию, при этом сочетая свойства обоих компонентов и взаимно усиливая их. Заключение. Полученные данные подтверждают перспективность дальнейшего исследования релиз-активных препаратов при нейродегенеративных нарушениях.Ключевые слова: амнезия, болезнь Альцгеймера, диваза, импаза, тенотен. Objective. On amnesia models induced by (icv) injection of β-amyloid fragment 25-35 peptide were evaluated antiamnestic actitity. Material and methods. It was used of active antibody preparations (RA AT) to protein S100 (tenoten), to eNOS (impaza) and combinations (divaza) antiamnestic activity behavioral tests novel object conditioned response passive avoidance. Results. Under the influence of RA AT S100 observed recovery of violation of the β-amyloid short-term memory (1 hour after the initial presentation of objects), and RA AT eNOS were more effective when tested 24 hours later. Combined medication completely compensate for the simulated deflection behavior of rats did not differ from the intact control. The CRPA RA AT S100 had the greatest impact on the LP entry into the dark compartment, and RA AT eNOS i...

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.

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.

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