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.

[Influence of magnesium deficiency correction on the effectiveness of bronchial asthma pharmacotherapy in children].

We have performed 24-week open-labeled comparative randomized parallel-group study of the basic therapy efficacy of uncontrolled and partly controlled atopic asthma children with magnesium deficiency. The additional correction of magnesium deficiency increases the efficacy of atopic asthma basic therapy. It leads to more pronounced inhibition of local allergic inflammation in respiratory system, decreases the exacerbation frequency (9.5%, p = 0.02), and increases the number of asymptomatic days and the 12-week constant asthma control frequency (71.4%, p = 0.145) as compared to the group without magnesium deficiency correction.

Experimental study of the effects of Dietressa, a new weight-reducing drug.

The capacity of a new drug containing ultra-low doses of antibodies to cannabinoid receptor type 1 (Dietressa) to reduce body weight gain in mice on a high-calorie diet was evaluated, possible mechanisms of drug action were analyzed, and its safety (abuse potential in the reaction of self-stimulation) was evaluated. Dietressa was not inferior to sibutramine in reducing body weight gain in mice and exhibited no abuse potential.

[Pharmacological neuroprotection against brain damage in ischemiai/reperfusion experiment].

Experiment carried out on laboratory animals (rats) were aimed at comparative evaluation of the effect of several neuroprotective drugs under the conditions of model brain ischemia-reperfusion. The experimental methods included staining of brain tissue sections by hematoxiline-eosine, Nissl staining, and expression of NOS1, NOS3, TRAIL by imunnohistological means. The intensity of damage in various parts of brain and the nature of apoptosis without neuroprotection and with popular neuroprotectors (cytoflavin, actovegin, mexidol) and a test drug at the stage ofpreclinical trial (AKF-90-7) were evaluated. Characteristic cytotoxic (coagulative pycnomorphic and colliquative necrosis of neurons) and vascular (hemostasia, erythropedesis) changes were revealed. The neuroprotective effectof drugs decreases in the following order: AKF-90-7 > cytoflavin > actovegin > mexidol.

[New approaches in correcting disorders of higher integrative brain functions in the pharmacotherapy of arterial hypertension with propranolol]. / Novye podkhody k korrektsii narushenii vysshikh integrativnykh funktsii mozga pri farmakoterapii arterial'noi gipertenzii propranololom.

In experiments on rats it is found that propranolol in a dose of 2 mg/kg has a negative effect on higher integrative functions of the brain. Nootropics--pyracetam (200 mg/kg), AKF-94 (20 mg/kg), PIR-87-6-O (50 mg/kg) and actoprotector bemityl (40 mg/kg)--normalized orientative-trying behavior, memory, and emotionality of the animals. A possible mechanism of the drug action and prospects of their clinical application are discussed.

[The EAA-ergic modulation of the brain dopaminergic system as a basis for creating new nootropic agents with stress-protective activity]. / VAK-ergicheskaia moduliatsiia dofaminergicheskoi sistemy mozga kak osnova sozdaniia novykh nootropnykh sredstv so stress-protektivnoi aktivnost'iu.

The paper provides theoretical evidence for and practical confirmation of the possible use of three lipophilic derivatives of N-acetyl-aspartic acid (EAA-AKF-94; AKF-92-10, and PIR-87-6-0). These compounds were shown to display pronounced nootropic activity to correct behavioral, memory, and cognitive disorders in rats exposed to emotional stress. Evidence is provided for the fact that modulation of monoaminergic brain activity mediated by heterosynaptic activation of EAA receptors.

[The stress-protector properties of new analogs of mediator amino acids]. / Stressprotektornye svoistva novykh analogov mediatornykh aminokislot.

Stress-protective effect of phosphonglycerid and acyl analogs of neurotransmitter amino acids, which displayed nootropic activity was obtained. These compounds exerted positive influence on behavioral failure and morphological statement after 18-h immobilization. Dilithium-N-acetyl-L-aspartic acid (AKF-94) and di(3-dimethoxyphosphorylpropyl) ester of N-acetyl-DL-aspartic acid (PIR-87-6-0) displayed the most expressive activity. Previously activating influence of these compounds at excitatory amino acid transmission had been shown. We supposed participation of this way in stress-protective effect of new compounds.

[Effect of GABA and piracetam on cerebral circulation and the neurogenic mechanisms of its regulation]. / Vliianie GAMK i piratsetama na mozgovoe krovoobrashchenie i neirogennye mekhanizmy ego reguliatsii.

Resistography was applied in acute cat experiments to study the effects of GABA and piracetam on the neurogenic pressor vascular reactions of cerebral and hind limb vessels, induced by stimulation of bulbar structures (locus coeruleus field), of the cervical sympathetic and tibial nerves. GABA (50 mg/kg) and piracetam (100 mg/kg) reduced the central and reflex evoked contractions of the cerebral vessels but enhanced their reflex evoked reactions. A possible mechanism of such drug actions is discussed.