Consequently, the amount of NO formed in the liver tissues was larger when mexidol was used. Evaluation of the EPR spectra of samples incubated with mexidol and management samples incubated beneath the identical circumstances confirmed, that NO was formed in liver tissue samples after incubation in the presence of mexidol. In liver tissues, nearly all cells are capable of expressing iNOS hepatocytes, Kupffer cells, endothelial cells, Ito cells; due to this fact, the increase in NO manufacturing in liver tissues shall be greater and extra easily noticed comparing to coronary heart tissues. Mexidol may have an effect on the activity of iNOS in vascular endothelial cells since in these cells inducible iNOS additionally capabilities in addition to constitutive endothelial NO synthase. Desk 1. Intensity change signals in iron-sulfur proteins.

Created an antihypoxant mexidol, which is a succinate antioxidant emoxipine. Expressed antihypoxic activity have individual representatives of a group of so-referred to as power-producing compounds, especially creatine phosphate, which supplies anaerobic resynthesis of ATP during hypoxia. Preparations of creatine phosphate (neoton) in high doses (about 10-15 g per 1 infusion) have been useful in myocardial infarction, important heart rhythm disturbances, ischemic stroke. ATP and other phosphorylated compounds (fructose-1, 6-diphosphate, glucose-1-phosphate) exhibit low antihypoxic exercise resulting from near full dephosphorylation in the blood and entry into cells in an power-poor kind. To grasp the character of cytostatic and cytotoxic indicators, it is necessary to think about reactions with oxygen and superoxide radicals. The products of these reactions are peroxynitrites and are chargeable for the toxic results of nitrogen oxide (NO). ]. ribonucleotide reductase, interplay with thiols, and depletion of energy reserves at present discussed as possible pathways for cell demise.

The primary extremely efficient antihypoxants were created within the 60’s. The primary drug of this type was gutimine (guanylthiourea). In the modification of the molecule of guatimine, the special significance of the presence of sulfur in its composition was proven, since its replacement with O2 or selenium completely removed the protecting effect of guatimine during hypoxia. This is also evidenced by a decrease in the incidence of cerebral disorders and the syndrome of multiple organ failure in complicated antihypoxic therapy. Probucol is currently one of the few reasonably priced and cheap home antihypoxants, which trigger a moderate, and in some circumstances, significant discount in the content material of cholesterol (CS) within the serum.

Within the nervous tissue itself, in pathological conditions, processes can take place that are to a sure extent analogous to adaptation-trophic modifications on the periphery. They are realized by the use of monominergic programs of the mind, originating from the cells of the brain stem. In some ways it’s the functioning of autonomic centers that determines the course of pathological processes in critical states in the postresuscitation period. Recently, the substituted dipeptide N-phenylacetylglycyl-L-proline ethyl ester (GZK-111), which is metabolized in vivo to cycloprolylglycine (CPG), which is equivalent to an endogenous cycloneuropeptide, was designed and synthesized at V. V. Zakusov Institute of Pharmacology. GZK-111 possessed all activities characteristic of CPG (nootropic, site (https://pipewiki.org/) anxiolytic, antihypoxic, neuroprotective, and analgesic) after intraperitoneal administration to rodents at doses starting from 0.1 to 5 mg/kg. The current work confirmed that GZK-111 also preserved its pharmacological results after peroral administration.

The antihypoxic impact was stereospecific as a result of the D-enantiomers have been inactive. These compounds at concentrations of 10-7 – 10-5 M also exhibited neuroprotective exercise for SH-SY5Y human neuroblastoma cell culture with 6-hydroxydopamine neurotoxicity. The methylamide and analogous free acid of N-phenylacetylglycylproline could not be cyclized into cycloprolylglycine and were inactive. It was concluded that the activity of the substituted glyprolines was associated with their conversion into cycloprolylglycine. Mexidol has been used in combination with fundamental therapy in 65 patients with mental disorders of natural genesis. The patients were handled during 56 days in accordance with a special scheme together with the drug intake and intramuscular and intravenous injections. Mexidol exerted a constructive effect on affective sphere, normalized the sleep-wake cycle, promoted rehabilitation of cognitive function thus enhancing the worldwide clinical state of patients. Marked and significant improvement was present in forty,zero% and 33,8% of circumstances, respectively. No extreme aspect-effects had been noticed.