[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.

Preclinical Toxicological Study of Release-Active Preparations for Prediction of Their Pharmacological Activity and Side Effects.

We studied chronic toxicity of a few release-active preparations: Dietressa (release-active preparation of affinity-purified antibodies to type 1 cannabinoid receptor), Divasa (releaseactive preparation containing a combination of affinity-purified antibodies to brain-specific S-100 protein and endothelial NO-synthase), Cardostin (release-active preparation containing a combination of affinity-purified antibodies to C-terminal fragment of angiotensin II type 1 receptor and endothelial NO-synthase), and Bation (release-active preparation containing a combination of affinity-purified antibodies to IFN-γ and CD4). We evaluated not only side and toxic effects, but also the relationships between these effects and pharmacological activities of the preparations. The data of preclinical toxicological studies of the release-active preparations can be used for prediction of their pharmacological activity.

The Use of Release-Active Antibody-Based Preparations for Vertigo Prevention in Adults.

The effectiveness of antibody-based release-active preparations Impaza (antibodies to eNOS), Tenoten (antibodies to brain-specific protein S-100), Dietressa (antibodies to type 1 cannabinoid receptor), Brizantin (combined preparation, antibodies to brain-specific protein S-100 and type 1 cannabinoid receptor), and Divaza (combined preparation, antibodies to brain-specific protein S-100 and eNOS) in the prevention of vertigo was studied on the model of intermittent accumulation of Coriolis accelerations (ICCA). Modification of activity of vestibular receptors and signal systems by release-active preparations contributed to an increase in ICCA tolerance time. Combined preparation Impaza possessed the most significant antinaupathic properties. Brizantin was less potent in this respect.

Anxiolytic and Antidepressant Effects of Divaza and Brizantin.

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.

[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.

Experimental study of the efficiency of Dietressa preparation on body weight reduction in mice feeding high-fat ration.

We studied the efficiency of Dietressa on body weight reduction in C57Bl/6 male mice feeding standard high-fat ration (24%). After 5-month daily intragastric administration of Dietressa, body weight gain was the lowest in comparison with other groups and did not differ from that in mice receiving the reference substance sibutramine for 5 months. In contrast to sibutramine, Dietressa did not increase motor activity of animals in the open field test and produced no anorectic effect. The mean body weight gain per each 1000 kcal of consumed food in the group of animals receiving Dietressa was lower than in the control group and mice receiving sibutramine.

Some aspects of toxicological activity of kardosten after chronic 6-month administration to rats.

Chronic treatment of rats with kardosten for 6 months had a positive effect on some ECG values and behavior without disordering the hepatorenal functions. All effects of the drug observed during a course of treatment were leveled and the parameters reached the basal values within 2 weeks after drug discontinuation, this confirming its safety.

Application of ultralow doses of antibodies to interferon-gamma in complex therapy of bacterial infections and prophylaxis of bacterial complications.

Comparative placebo-controlled clinical trials on the efficiency and safety of ultralow doses of antibodies to human IFN-gamma (anaferon pediatric formulation and anaferon) and prophylaxis of bacterial complication showed that administration of these preparations in complex therapy of bacterial infection reduced the incidence of bacterial complications of viral infections and considerably decreased the duration of the main clinical symptoms of the disease.

Clinical study of the efficiency and safety of afala in patients with benign prostatic hyperplasia.

The use of afala in patients with benign prostatic hyperplasia and moderate urination disturbances reduced the symptoms of the disease, improved urodynamic parameters, and increased quality of life. Clinical efficiency of afala was comparable with the efficiency of Serenoa repens extract (reference preparation).

Evaluation of the efficiency and safety of combined treatment with impaza and nitrates in CHD patients with erectile dysfunction.

The safety of combined administration of ultralow doses of antigens to endothelial NO synthase (impaza) and nitrates for the treatment of erectile dysfunction in CHD patients was evaluated in an open non-comparative clinical trial. The efficiency and safety of impaza and the possibility of its administration to patients receiving nitrates were demonstrated.

Efficiency and safety of long-term artrofoon treatment in rheumatoid arthritis.

In patients with rheumatoid arthritis, prolongation of artrofoon therapy to 2 years led to maintenance of the positive clinical effect attained after 6-month treatment. Moreover, significant improvement was observed by some parameters (integral pain intensity, swelling index, Ritchie articular index, morning stiffness, and articular score). No side effects related to artrofoon treatment were observed throughout the treatment period in the main group. The results indicate high efficiency and good tolerability of the preparation and attest to advisability of its long-term use.

Effect of impaza on cardiovascular system.

Experiment on ISIAH rats showed that antibodies to endothelial NO synthase in ultralow doses (impaza) produced a mild and progressive antihypertensive effect slightly inferior to that of losartan. The use of impaza is perspective in patients with erectile dysfunction and cardiovascular pathology.

Experimental study of hypotensive effect of kardos in rats with inherited hypertension.

Kardos, a preparation containing ultralow doses of antibodies to C-terminal fragment of type 1 receptor of angiotensin II, intragastrically administered to SHR rats with hereditary hypertension for 28 days reduced blood pressure by 14.8%. Kardos was not inferior to losartan and, in contrast to the latter reduced HR by 9.4%.

Nootropic and antiamnestic effects of tenoten (pediatric formulation) in immature rat pups.

The antiamnestic effects of tenoten (pediatric formulation) was demonstrated on the model of scopolamine-induced amnesia of passive avoidance reflex and the nootropic effect of this preparation was demonstrated on the model of incomplete conditioning and in rat pups with experimental attention deficit syndrome. The efficiency of the preparation was comparable to that of piracetam and phenibut and even surpassed it by some parameters.

Antiaggressive activity of antibodies to S-100 protein in ultralow doses.

Experiments on rats demonstrated antiaggressive activity of ultralow doses of antibodies to S-100 protein in tests of motivated and unmotivated aggression. The effect of ultralow doses of antibodies to S-100 protein in single and course treatment was not inferior to that of benzodiazepine anxiolytic diazepam.

Study of the effects of preparation containing ultralow doses of antibodies to S-100 protein in experimental hemorrhagic stroke.

Ultralow doses of antibodies to S-100 protein increased rat survival, reduced neurological deficit, eliminated myorelaxation, and improved movement coordination and cognitive functions in rats with experimental hemorrhagic stroke; the efficiency of the preparation was not inferior to that of nimodipine. In contrast to nimodipine, ultralow doses of antibodies to S-100 protein exhibited pronounced anxiolytic properties.

Effect of ultralow doses of antibodies to S-100 protein in animals with impaired cognitive function and disturbed emotional and neurological status under conditions of experimental Alzheimer disease.

Course administration of ultralow doses of antibodies to S-100 protein restores cognitive functions and neurological status, improves emotional state, and reduces anxiety in animals with modeled Alzheimer disease based on cholinergic system deficiency caused by subchronic treatment with scopolamine.

Antiulcer activity of preparations containing ultralow doses of antibodies in modeled chronic ulcer in rats.

Screening of three potential antiulcer preparations containing ultralow doses of antibodies to endogenous regulators of ulcer formation (gastrin, histamine, and H2 histamine receptors) on the model of acetic acid-induced gastric ulcer in rats revealed pronounced antiulcer effect of ultralow doses of antibodies to histamine. The dynamics of regeneration of the ulcer focus by morphological and histological characteristics was similar during treatment with ultralow doses of antibodies to histamine and with famotidine.

Effects of preliminary administration of haloperidol in low doses on the effects of haloperidol on behavioral reactions and command neuron membrane potential in edible snail.

We studied the effects of preliminary administration of haloperidol in low doses on changes in motor activity of edible snail and in electrical properties of defensive behavior command neurons induced by chronic administration of haloperidol. The rate of locomotion decreased after injections of haloperidol preparations (C6, C12, C30, C200 and a mixture C12+C30+C200) for 3 days. Similar changes were observed after 3 days of haloperidol administration. Haloperidol preparations in low doses produced a modulating effect on the decrease in locomotion rate and hyperpolarization of command neurons in edible snails caused by chronic exposure to haloperidol: the decrease in locomotion rate caused by chronic haloperidol treatment was prevented by preliminary injection of haloperidol in low doses C6, C12 and C30; the depolarizing shift of command neuron membrane potential was also abolished after consecutive injection of the same haloperidol preparations C6, C12 and C30.

Involvement of the GABA-B system in the mechanism of action of ultralow-dose antibodies to S-100 protein.

The involvement of the GABA-B neurotransmitter system in the realization of anxiolytic and antidepressant activities of ultralow-dose antibodies to S-100 protein is demonstrated. Simultaneous injection of ultralow-dose antibodies to S-100 protein and GABA-B receptor agonist baclofen reduced the anxiolytic and antidepressant effects of the drug, while GABA-B receptor antagonist faclofen stimulated the anxiolytic and reduced the antidepressant effect of ultralow-dose antibodies to S-100 protein. The effect of ultralow-dose antibodies to S-100 protein on the GABA-B-ergic system differs from that of benzodiazepine anxiolytics (diazepam) and tricyclic antidepressants (amitryptiline) not affecting this transmitter system.