Resume. Reviewed phenomenology of food-drug interactions, pharmacokinetic and other targets of this interaction. The attention is focused on possible genotoxic adverse events by food-drug interactions.

On culture of hippocampal HT-22 cells line it is shown that dimeric dipeptide mimetiks of different Loops of NGF realize their action via specific neurotrophic TrkA-receptor and selective activate post-receptor intracellular signal ways. Mimetiks of 1th (GK-6 (10-6M)) and the 3rd Loops (GTS-115 ((10-6M)) evoke activation of two main signal cascades - PI3/Akt and MAP/Erk, while mimetic the 4th loop of NGF (GK-2 (10-8M)) only one - a PI3/Akt-way.

We have studied the effects of lithium ascorbate on the Wistar male albino rats using a dose of 1 000 mg/kg. The concentration time curves for whole blood and tissue homogenates of 10 different biological substrates were derived (the brain, the frontal lobe of the brain, heart, aorta, lungs, liver, kidneys, spleen, adrenals, femoral bone). In the framework of the tubeless analysis of the concentrations in whole blood dynamics the following values of pharmacokinetic parameters of lithium ascorbate were obtained: C_max=50,59 |±g/l, T_max=1,50 h, Clast=33,7 |±g/l, AUCt=1 750 |±g/l*h, MRTt = 22,9 h, Lz=0,005 1/h, T_1/2=141 h, CL = 0,029 l/h, VD=5,9 l. The concentration of lithium in whole blood and in the frontal lobe of the brain remained stable for at least 40...45 hours after the concentration peak. Multicompartment pharmacokinetic analysis showed that the stabilization of the levels of lithium in the blood and in the brain is supported by a special lithium pool, reportedly consisting of adrenal glands, aorta, femur and brain.

We studied the pharmacokinetic parameters of N-acetylcysteine at a single oral and intravenous administration of healthy volunteers. Elimination half-life (t_1/2) within 2 hours and the maximum concentration in blood (C_max) after 1 hour after administration was more than 10 times higher when intravenous on a comparison with oral administration. Effect of exchange rate on intravenous administration of N-acetylcysteine (1 200 mg/day for one week) the concentration of endogenous aminothiols in patients with diseases that are accompanied by oxidative stress (ischemic stroke and vascular complications of diabetes mellitus) are also studied. In ischemic stroke example it shows that the concentration of cysteine in plasma was increased by 1,6 times, and homocysteine levels did not change, as the ratio of reduced and oxidized cysteine (CysSH / CysSSCys). The content of total and free glutathione in red blood cells was not significantly changed, but significantly increased GSH / GSSG ratio, characterizing the antioxidant capacity of cells. We conclude that the inclusion in the scheme of N-acetylcysteine therapy of these diseases, accompanied by a more favorable clinical outcome due to a significant increase in antioxidant capacity of cells and tissues.

Effects of intraperitoneal and intranasal administration of peptides noopept (1 mcg/kg/day for 5 days) and semax (0,6 mcg/ kg/day for 5 days), known to produce nootropic and anxiolytic actions were tested in BALB/c mice (the Line is characterized by Lowered exploratory efficacy and elevated anxiety) by the use closed exploratory cross maze. Both semax and noopept using both routes of administration produced nootropic and anti-anxiety activity. In case of intraperitoneal administration of both peptides the anti-anxiety effect was more prominent, while after intranasal treatment the elevation of exploratory behavior was better seen. The discrepancy between the mice behavior after different routes of the peptides can be attributed to differences in pharmacokinetics, biotransformation and dynamic anxiolytic and nootropic activity of the drugs.

He aim of the study was to investigate the influence of a derivative of 4-benzoyl pyridine connection, GIZ-298 on electroencephalographic manifestations ranvulsive activity in the brain structures of rats with cobalt-induced focal epilepsy in the first stage of the formation of epileptic system. Methodology of the study. We used the technique of creation (by an application of cobalt to the brain of rats) chronic epileptogenic focus, generating paroxysmal activity in different brain structures: the ipsi- and contralateral cortex, hippocampus and hypothalamus. The results of the study. Established that injection ofGIZ-298 at a dose of 60 mg/kg (intraperitoneally, once) on the first stage of development of the system eliminates epileptic EEG manifestations of seizure activity in all the investigated structures of the brain, with the greatest efficiency in the ipsilateral cortex and the hypothalamus, significantly reducing both the number and duration of seizure discharges.

The development of morphine-induced antinociceptive tolerance limits its therapeutic efficacy in pain management. Effects of non-benzodiazepine anxiolytics ladasten and GB-115 on the development of antinociceptive tolerance to morphine were studied in albino male rats. The tolerance was induced by daily sub-chronic administration of morphine (2,0 mg/kg, i.p., twice daily for 5 days) and assessed in immersion tail-flick test on days 1 and 5. Concomitant sub-chronic administration of dipeptide anxiolytic GB-115 (0,1 mg/kg/5 days, i.p.), developed on the base of endogenous tetrapeptide cholecystokinin (CCK), followed by morphine (2,0 mg/kg), reversed the antinociceptive tolerance to morphine on day 5. GB-115 per se at the same anxiolytic dose demonstrated a short-term analgesic activity on days 1 and 5. In contrast, 2-aminoadamantane derivative Ladasten (50,0 mg/kg/5 days, i.p.) with psychostimulant and anxiolytic activity, failed to do so. Ladasten at dose employed in the study, did not exert any effects on pain threshold on days 1 and 5. Our results suggest that in this well-characterized model of acute somatic pain, the development of tolerance to the antinociceptive effect of systemic morphine can be prevented by co-administration with GB-115.

In the model of peritonitis in mice induced by intraperitoneal injection of acetic acid the main metabolite of afobazole M-11 at doses of 1, 5 and 10 mg/kg per os reduces the intensity of the exudative stage of inflammation, but at doses of 20 and 40 mg/kg it exhibits no anti-inflammatory activity. The anti-inflammatory activity of M-11 at doses of 1, 5 and 10 mg/kg is less pronounced compared with diclofenac sodium 10 mg/kg. Evaluation of the influence of M-11 on visceral pain induced by inflammation demonstrated that the main metabolite of afobazole does not exhibit analgesic activity.

The study of chronic toxicity injection form afobazol with daily intravenous administration for 2 weeks old female and male rats in doses of 0,1; 1; 5 and 50 mg/kg, female and male rabbits at doses of 0,1; 1 and 10 mg/kg. A detailed clinical and laboratory examination did not reveal any toxic effects of the drug in doses of 0,1 - 5 mg/kg. Afobazol when administered intravenously in doses of 10 mg/kg for rabbits and 50 mg/kg in rats induced clonic convulsions, and intermittent loss of coordination of movement, and at the same dosage segment PQ increased in female rats. Afobazol 10 and 50 mg/kg increased levels of glucose and total protein in laboratory animals and decreased the content of urea in blood serum of rats. Investigation showed allergenic properties afobazol in doses of 5 and 50 mg/kg did not cause allergic reactions of immediate and delayed type reactions and pseudoallergic. The slight increase in allergic reactions to foreign protein when administered afobazol indicates the possibility of individual sensitivity in people with protein sensitization.