The purpose of this study - search among the benzoylamino (phenyLsuLfonyL) amino-substituted cyclic aminoacids derivatives biologically active compounds exhibiting properties of the zinc-dependent metaLLproteinases 2nd and 9th type blockers which is known to pLay a key roLe in the pathogenesis of the myocardium earLy post-infarction remodeLing. In studying the effect of newLy synthesized compounds on metaLLoproteinase-9 LeveLs in bLood of rats with acute myocardiaL infarction were seLected compound Leader: 1-({4-[(4-chLorobenzoyL)amino]phenyL}suLfonyL-L-proLine, which effectiveLy bLocked the increase of this enzyme Level. Using echocardiography it was demonstrated that the seLected compound-Leader prevents the myocardiaL remodeLing deveLopment in the acute phase of experimentaL myocardiaL infarction, at Least not inferior to the reference inhibitor of metaLLoproteinases - doxycycLine.

In two animaL modeLs of parkinsonian syndrome - induced by 1-methyL-4-phenyL-1,2,3,6-tetrahydropiridine (MPTP) in C57BL/6 mice and 6-hydroxidopamine (6-OHDA) in rats noveL antiparkinsonian drug hemantane was shown to reduce the increase of brain LeveL of Lipid peroxidation caused by both neurotoxines. In prefrontaL cortex and striatum of mice which were treated with hemantane 10 mg/kg 5 days before MPTP and 5 days together with MPTP and in rats which received hemantane during 21 days after 6-OHDA injection in mediaL forebrain bundLe the LeveLs of maLondiaLdehyde and conjugated dienes were significantLy Lower than in untreated animaLs. The data obtained is consistent with antioxidant properties of hemantane.

He paper presents the results of studies of Lithium ascorbate on the models of stress in vitro and in vivo. The results show significant neuroprotective effect of Lithium ascorbate on the model of glutamate stress in the culture of grainy neurocytes. Experiments on modeLs of transport and immobiLization stress confirmed the adaptogenic effects of Lithium ascorbate.

ResuLts of precLinicaL pharmacodynamic and pharmacokinetic study of tropoxine (a new originaL antimigraine drug) after singLe intravenous administration in rats were presented. Tropoxine in significant extent suppresses constricting reactions of rat brain vesseLs, serotonin, and agonist of 5НТ_2В/2С receptors. Direct reLationship between tropoxine concentrations decreasing in the rat bLood pLasma and changing of the brain circuLation associated with serotonin and m-chLorphenyLpiperazine.

Dimeric dipeptide mimethic human nerve growth factor, bis-(N-monosucciniL-gLycyL-Lysine), GK-2h at doses 0,1, 0,5, 1,0, 1,5 mg/kg, i.p. has an antiamnesic effect on the modeLs of scopoLamine, maximaL eLectroshock or ketamin induced passive avoidance response amnesia. GK-2h at doses 1,0-1,5 mg/ kg possess weak antihypoxic und anticonvuLsive properties, it does not affect the expLoratory behavior of animaLs in the test of open fieLd.

The study of the neuroprotective properties new original compound GIZH-276 and evaluate changes activities of prolyl endopeptidase (PEP) and lactate dehydrogenase (LDH) in blood plasma of rats with post-traumatic hematoma (model of hemorrhagic stroke) is the aim of this investigation. Methodology of the study: Modeling of hemorrhagic stroke (HS) was carried out using the creation of intracerebral post-traumatic hematoma with the introduction of autologous blood into the site of injury. Assay of enzymes activities in plasma was carried out with fluorescent (PEP) and ultraviolet (LDH) methods. The results of the study: GIZH-276 at dose of 10 mg/kg (7 days, intraperitoneally) has a pronounced neuroprotective effect, attenuating neurological deficits in rats with hemorrhagic stroke 24 hours, 7 and 14 days after surgery and statistically significantly increasing the number of surviving rats by 14 days of observation. The weakening of neurological deficit and death of animals is accompanied by decreased activity of enzymes LDH and PEP, which indicates the improvement of security of brain tissue oxygen and reducing neuroinflammation. Conclusion: Safety and neuroprotective effect of GIZH-276 on the model of hemorrhagic stroke may be partially due to positive effect on inflammatory and hypoxia during the development of secondary brain damage in stroke.

Pharmacological activity of dimeric dipeptide mimetics of the nerve growth factor loops 3 and 4, correspondingly GTS-115 and GK-2, was studied in a model of ischemic stroke, induced by transient middle cerebral artery occlusion in rats. The both compounds, at i.p. subchronic administration (0,5-1 mg/kg/day, 7 days, beginning at 4 hours after surgery), significantly reduced cerebral infarct volume as was estimated by morphometry of 2,3,5-triphenyltetrazolium chloride (TTC) -stained brain slices: GTS-115 by 25% and GK-2 by 35%. Mimetic of NGF loop 4 (GK-2), which is the most active compound, was selected for further development as a potential therapeutic agent.

In the previousLy deveLoped transLation modeL of aLcohoLic cardiomyopathy in white nonLinear rats was studied the cardioprotective effects of trimetazidine and fabomotizoLe hydrochLoride that were injected daiLy during the 25th - 28th weeks of continued consumption of 10% ethanoL It is shown that trimetazidine (30 mg/kg/day i.p.) and fabomotizoLe hydrochLoride (15 mg/kg / day i.p/) in the above conditions, significantLy reduced the remodeLing of the Left and right ventricLes of the heart and increased the heart contractiLe function.

Antiparkinsonian, anti-inflammatory and analgesic activity of ADK-1058, a metabolite of hemantane, was investigated in comparison with hemantane at the effective dose of 20 mg/kg. ADK-1058 exhibits a minor antiparkinsonian effect by reducing the severity of oLigokinesia in C57BL/6 mice with MPTP-induced parkinsonian syndrome. ADK-1058 exhibits anti-inflammatory activity in the model of acetic acid peritonitis, but has no analgesic effect in visceral or somatic pain in mice. Effects of ADK-1058 at the dose of 20 mg/kg do not exceed antiparkinsonian, anti-inflammatory or analgesic effects of hemantane at the dose of 20 mg/kg.

The estimates of the neurophysiological, pharmacokinetic, hemodynamic and anti-inflammatory properties of ascorbate anion were obtained. In comparison with the control molecules (nicotinate, oxybutyrate, comenate, carbonate) ascorbate anion has characteristically higher affinity for serotonin, dopamine, benzodiazepine, adrenergic receptors. Higher affinity for human benzodiazepine receptor indicates possible anxiolytic effects of ascorbate. Ascorbate anion can be characterized by a strong antioxidant and anti-inflammatory effect caused by modulation of prostaglandin metabolism. Ascorbate anion can also exhibit anticoagulant, antihyperglycemic and antihyperlipidemic effects. Chemoreactome simulation results also indicated that carbonate anion has none of the aforementioned properties of ascorbate anion.

The purpose of this study is to evaluate the chronic toxicity of the drug dilept upon a daily orally administration for 6 months at doses of 16 and 160 mg/kg. Detailed clinical and laboratory examinations did not reveal any chronic toxic effect in animals except for reversible dystrophic changes in heart, kidneys, liver, reversible high level of creatinine in urine and degenerative forms of red blood cells in rats treated with drug at dose 160 mg/kg. Evaluation of anti-inflammatory properties of dilept in the inflammatory reaction induced by concanavalin A showed that at doses of 0,1 and 10 mg/kg i.p. in mice led to a significant suppression of the inflammatory response. Study showed that dilept has no allergenic properties.