[NO-dependent mechanisms of cardioprotective activity of MT preparation during course administration to SHR rats].

Chronic (15 days) single daily intraperitoneal insertion of the new preparation MT (5 mg/kg) and metoprolol (10 mg/kg) into SHR rats leads to the same decrease (18%) in arterial pressure. In addition, MT exhibits a cardioprotective effect because of NO-mimetic properties, increasing NO formation in myocardium via increasing general NOS activity and eNOS expression. MT normalizes iNOS expression in myocardium mitochondria and decreases nitrotyrosine (nitrosation stress marker) formation. At the same time, the reference preparation metoprolol did not exhibit NO-mimetic properties in myocardium of SHR rats.

[Influence of ademol on NO metabolism indices in rats with modeling myocardial infarction].

It was established in experiments on the rats in the acute period of modeling pituitrin-isadrin myocardial infarction the formation of nitrogen monoxide decreases along with its accelerated transformation into peroxynitrite. It was evidenced by more than double inhibition of NO synthase activity in the myocardium and by decreasing the amount of nitrates on the background of the increasing level of peroxynitrites' marker--nitrotyrosine by 246.6% at an average. Experimental therapy of rats by ademol which is a derivate of adamantan (1-adamantiloxy-3-morpholino-2 propanol hydrochloride) better than by corvitin normalizes the processes of synthesis of nitric oxide. At the same time ademol probably exceeded the reference drug in ability to increase NO synthase activity and amount of nitrate, and promoted a decrease of the level of nitrotyrosine in the myocardium on the average by 36.3; 50.6 and 12.7%, respectively. Corrective influence of ademol on indicators of metabolism in NO system under the conditions of acute cardiac ischemia indicates to promicing development of domestic cardioprotector on its base.

[Antioxidant and cerebroprotective action of N-,S-chinazolone derivative under rat brain ischemia].

Under modelling of brain ischemia in rats the antioxidant and cerebroprotective action of new N-,S-chinazolone derivative--compound NC-224 has been established. The compensation of pathobiochemical abnormalities in the system "LPO-antioxidant protection" is observed, indicators of carbohydrate metabolism and energy-supply, and morpho-functional status of brain cells are improved under administration of the compound NC-224. Administration of the compound NC-224 to rats promoted a decrease of the lethality index and signs of neurological deficiency.

[Antioxidant activity of condensed [1,2,4]-triazinone derivatives in nitrosative stress].

Antioxidant activity of nine [1,2,4]-triazinone derivatives was studied in the work. Our data show that [1,2,4]-triazinone derivatives with benzyl alcohol, propyl alcohol, me-thyl alcohol and tolyl residues in their structure have antioxidant activity in condition of in vitro NO formation. KO-17 compound proved to have the greatest antioxidant activity which exceeded N-acetyl cysteine's one.

[Pharmacological correction of neuronal damage in sensomotor zone of frontal cortex under conditions of experimental cerebral blood flow pathology].

The administration of thiotriazoline, emoxypine and magnelong (a combined glycine-magnesium preparation) to animals with acute cerebral circulatory insufficiency showed significant neuroprotective effect in both acute and late ischemic periods, as indicated by the indices of cell density and number and the characteristics of apoptic and destructed neurons approaching those in the group of intact rats. Pyracetam showed cerebroprotective effect only in late ischemic period. Magnelong exhibited the most significant neuroprotective effect, maintaining cell density on the intact control level and reducing the number of apoptotic and destructed neurons.

[Pharmacological neuroprotection against experimental acute cerebral ischemia of neurons of sensomotor area of frontal cortex and hippocampus in rats].

Emoxypine, thiotriazoline, and NN-103 (a 4-hydrazinoquinasoline derivative) exhibit a pronounced neuroprotective action during acute cerebral stroke. Emoxypine and thiotriazoline are more effective in inhibiting death of neurons in the sensomotor area of the frontal cortex, while NN-103 is more active in the hippocampus. The ischemic death of neurons in the sensomotors area of the frontal cortex with equal probability takes place by karyopyknosis or cytolysis, while in the hippocampus, mainly by cytolysis. All preparations (except for piracetam) with antioxidants properties are powerful membranoprotective agents, which is confirmed by a considerable decrease in the rate of cytolysis both in the cortex and in the hippocampus. The use of piracetam in the case of acute cerebral stroke increases the rate of neuronal death in various areas of the cortex, up to complete destruction of nerve tissues with the formation of cysts (in hippocampus). The tested preparations exhibit different mechanism of neuroprotection: emoxypine and NN-103 (in the sensomotor area of the frontal cortex and hippocampus) and thiotriazoline (in the hippocampus) produce the neuroprotection action on the background of increased activity of transmissions and transcription processes, while thiotriazoline (in the sensomotor area of the frontal cortex) offers neuroprotection on the background of inhibited transcription and transmission activity.