Comparative chemoreactome analysis of mexidol
Author:
I.YU. TORSHIN, O.A. GROMOVA, I.S. SARDARYAN, L.E. FEDOTOVA
Moscow Institute of Physics and Technology, Dolgoprudny. Russia; Ivanovo State Medical Academy of the RF Ministry of Health, Ivanovo, Russia
Summary:
Objective. To compare mexidol with control molecules (choline alfoscerate, piracetam, glycine, semax) using chemoreactome analysis. Material and methods. The chemical structure of mexidol was compared to molecule metabolites extracted from the Human Metabolome Database (HMDB) and a drug database. More than 40 000 of metabolites from HMDB were used as a model of human metabolome. Results and conclusion. The chemoreactome analysis showed that mexidol may be (1) an agonist of acetylcholine and GABA-A receptors; (2) an anti-inflammatory agent, the effects of which are carried out by inhibiting the synthesis of pro-inflammatory prostaglandins; (3) a neurotrophic agent with neuroprotective properties; (4) a coagulation inhibitor; (5) a diabetes medication and (6) a hypolipidemic agent. Compared to «control» molecules, mexidol has a more pronounced safety profile (a lower impact on serotonin, dopamine and adrenergic receptors, a lesser degree of interaction with the potassium channels of the heart, MAO and P450 cytochromes). The results of modeling allow to specify the mechanisms of action of mexidol at the molecular level.
Keywords: mexidol, neuroprotection, chemoreactome analysis, chemoinformatics, forecasting.
Mexidol effect on the factor induced by hypoxia HIF-1α expression in the rat cerebral cortex in its ischemia
Author:
E.N. YAKUSHEVA, P.YU. MYLNIKOV, I.V. CHERNYKH, A.V. SHCHULKIN.
Pavlov Ryazan State Medical University, Ryazan, Russia.
Summary:
The aim of the research – to study the Mexidol (ethylmethylhydroxypyridine succinate) effect on the factor induced by hypoxia (HIF-1α) expression in the frontal cortex of the brain in its ischemia. Material and methods. The work was performed on the 64 male Wistar rats. The expression of HIF-1α was determined immunohistochemically. Results and discussion. It is determined that single intraperitoneal administration of Mexidol at a dose 120 mg/kg and oral administration at a dose 100 mg/kg three times a day for 14 days is not affected the expression of HIF-1α. Unilateral occlusion of the common carotid artery increases the expression of HIF-1α at 4 hours after the occlusion. Oral administration of Mexidol at a dose 100 mg/kg three times a day for 14 days before and after ischemia increases the expression of HIF-1α after 4 and 12 hours in comparison with the norm, on the 5th day in comparison with occlusion control. Thus, it has been established that Mexidol increases the expression of HIF-1α in the frontal cortex of rat brain not under normal conditions, but in unilateral occlusion of the common carotid artery.
Keywords: mexidol, ethylmethylhydroxypyridine succinate, ischemia, occlusion of common carotid artery.
A comparative study of the effects of mexidolum and mildronatum on the physical performance of experimental animals
Author:
Т.А. VORONINA, I.G. KAPITSA, Е.А. IVANOVA.
Zakusov Institute of Pharmacology, Moscow, Russia.
Summary:
Objective. To evaluate the effects of mexidolum on physical performance using acute and subchronic administration in experimental animals. Materials and methods. The investigation was carried out using 123 male white outbred mice. The forced swim test was used to assess the effects of the drugs on the physical performance of mice. Results and conclusion. A single intraperitoneal administration of 50 and 100 mg/kg mexidolum and subchronic intraperitoneal administration of 100 mg/kg mexidolum significantly enhances the physical performance of animals in the forced swim test. Subchronic intraperitoneal administration of 100 mg/kg of the comparison drug mildronatum enhances the physical performance of animals, while intraperitoneal administration at a lower dose (50 mg/kg) has no effect. The effect of mexidolum at a dose of 50 and 100 mg/kg is comparable with the effect of mildronatum in a dose of 100 mg/kg.
Keywords: physical performance, mexidolum, mildronatum, mice.
The distribution of mexidol in the rat’s brain and its subcellular fractions
Author:
A.V. SHCHULKIN, E.N. YAKUSHEVA, I.V. CHERNYKH.
Pavlov Ryazan State Medical University, Ryazan.
Summary:
Objective: To study the penetration of mexidol through the blood-brain barrier into different brain compartments and cell mitochondria. Material and methods. The study was carried out on adult male Wistar rats using the drug mexidol (“Farmasoft” Russia). The penetration of mexidol into different compartments of the brain (the cortex, cerebellum, thalamus and medulla) and distribution between mitochondrial and cytoplasmic fractions of the cerebral cortex was studied. The concentration of mexidol in blood plasma and brain tissues was measured using HPLC. Results and Conclusion. Mexidol penetrated through the blood-brain barrier into brain compartments of rats with the maximal accumulation in the cortex. In the brain cortex cells, mexidol was identified in the cytoplasmic and mitochondrial fractions.
Keywords: mexidol, pharmacokinetics, blood-brain barrier, cortex, cerebellum, thalamus, medulla, mitochondria, HPLC.
Effect of mexidol on the development of the phenomenon of the neuronal excitotoxicity in vitro
Author:
A.V. SHCHULKIN.
Summary:
Effect of mexidol on the development of the phenomenon of the excitotoxic syndrome in vitro has been studied. Mexidol inhibits in vitro the development of glutamate-induced neurotoxicity, ascorbate-dependent (non-enzymatic) and NADPH2-dependent (enzymatic) iron-induced lipid peroxide oxidation, is able in high concentrations to bind superoxide anion-radical, significantly increases the activity of Se-dependent glutathione peroxidase, decreases the activity of induced NO-synthase and does not impact on the activity of glutathione-SH-transferase, catalase and neuronal NO-synthase. These effects underlie the antioxidant and antihypoxic action of the drug.
Keywords: mexidol, glutamate-induced neurotoxicity, lipid peroxide oxidation, superoxide dismutase, catalase, glutathione peroxidase, glutathione-SH-transferase, induced and neuronal NO-synthase.