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Taking into account the high efficacy of 2-arylpropionic acid derivatives among NSAIDs and based on their SARs, we have evaluated the anti-inflammatory, antinociceptive, and antiaggregant activity and ulcerogenic properties of a new synthesized non-protein amino acid (NPAA) derivative S(-)-2-amino-2-methyl-3-phenylpropanoic acid (NPAA-36). A new method of NPAA-36 synthesis was developed and experiments were carried out, which showed that this compound injected in a dose of 10 mg/kg (i.p.) inhibited xylene-induced ear oedema by about 31.1%, which proved its anti-inflammatory properties. The antinociceptive activity of NPAA-36 was assessed in tail-flick test by the ability to increase the tail cut-off latency by 36.78% within 60 min after injection at the same dose. Investigation of the ulcerogenic properties of NPAA-36 demonstrated that it exhibited lower gastrointestinal toxicity than a well-known arylpropionic acid derivative NSAID. Results of in vitro experiments showed the antiplatelet activity registered not in all (only in 41.2%) cases, which might imply lower bleeding. The obtained data indicate that the new NPAAderivative can be a potential basis for the development of new anti-inflammatory drugs with weak side effects.

The effect of α2-adrenoblocker mesedin (2-(2-methylamino-4-thiazolyl)-1,4-benzodioxane hydrochloride) on the content of oxidative stress biomarkers in the brain tissue was well studied in ischemic disorders. The aim of this study is to reveal the possible mechanisms of the antihypoxic effect of mesedin. The quantitative changes of the final product of lipid peroxidation (LP)—malondialdehyde (MDA) and carbonyl derivatives of proteins — aldehyde-dinitrophenylhydrazones of neutral character (ADNPuv), ketone-dinitro-phenylhydrazones of neutral character (KDNPuv), aldehyde-dinitrophenylhydrazones of basic character (ADNPvs) and ketone-dinitrophenylhydrazones of basic character (KDNPvs) were studied in the brain tissue of rats (n = 56) under the condition of experimental ischemia caused by the ligation of the right common carotid artery. The study showed that one of the possible mechanisms of antihypoxic action of mesedin is its ability to prevent the accumulation of malondialdehyde and to limit protein carbonylation in brain ischemia. The data received demonstrates that mesedin could serve as a potential medicine for the correction of cerebrovascular ischemic disorders, for the reason that along with improving cerebral blood flow and preventing the development of morphological shifts and neurobehavioral disturbances in brain local ischemia, the medicine also mitigates the aggressive action of oxidative stress while protecting the brain tissue from the consequences of hypoxia.

More than 50 years ago we demonstrated that the neurosecretory NSO and NPV cells of the hypothalamus can produce not only releasing hormones, such as vasopressin and oxytocin, but also hormones that are able to regulate cardiac activity and coronary circulation. Moreover, we showed that 5–6 min after intravenous administration (1 mg/kg) to a cat of a coronarydilatory protein of the hypothalamus that we isolated the blood pressure in the vertebral artery gradually decreased, reaching 20–30 ml of Hg following two or more administrations, thus indicating the reduction of cerebral vessel tonus. These results indicate that the protein we isolated is able to dilate the blood vessels of both the heart and the brain. Later, we isolated these proteins from animal neurohypophysis, which indicates the hormonal nature of these proteins and polypeptides. Moreover, the proline-rich polypeptides PRP-1 (Galarmin) that we isolated and chemically characterized as consisting of 15 amino-acid residues, has coronarydilatory properties. It was of great interest to investigate the activity of Galarmin on normal and damaged cerebral blood flow. Our experimental results demonstrated the ability of PRP-1 to repair damaged cerebral blood flow caused by common carotid artery occlusion.

The cerebral content of lactate and phosphate metabolites and intracellular pH were studied in intact rats 3 and 8 days after ligation of the middle cerebral artery. Each rat exhibited accumulation of lactate and individual changes in creatinine phosphate, inorganic phosphorus, and monophosphate esters, while the level of ATP, ADP, and pH were constant. Regulatory changes in the system of cerebral energy metabolism are characterized by the correlation analysis of these parameters.