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.
The results of the study of the efficacy and safety of mexidol in patients with chronic cerebral ischemia
Author:
E.I. CHUKANOVA, A.S. CHUKANOVA, KH.I. MAMAYEVA.
Pirogov Russian National Research Medical University, Moscow.
Summary:
Objective. To analyze the efficacy and safety of mexidol and their effect on the dynamics of neurological signs of the disease, emotional status and quality of life in patients with chronic cerebral ischemia (CCI). Material and methods. We studied 45 patients with CCI who received mexidol in dose 500 mg a day during 14 days by introvenal introduction with the following peroral administration in doses 500 mg twice a day during 60 days. A comparison group included 30 patients with CCI matched for age, risk factors and severity of neurological symptoms, who did not receive mexidol. Patients of both groups received standard treatment that included medications needed for the complete correction of the risk factors. Cognitive function (MMSE), movement activity and quality of life (SF-36) were assessed. Results. To the end of the study (74th day), a decrease in the severity of movement disorders, normalization of SF-36 scores and improvement of mean values of screening-assessment of cognitive function were identified in patients of the main group compared to those of the comparison group. Conclusion. The high efficacy and safety of treatment of CCI patients with mexidol using.
Keywords: chronic cerebral ischemia, oxidative stress, movement disorders, depression, quality of life, mexidol.
Contemporary paradigm of rational stroke treatment
Author:
S.A. ZHIVOLUPOV, YU.S. BUTAKOVA, I.N. SAMARTSEV.
Department of nervous diseases of the Military Medical Academy; primary vascular compartment Novodvinsk City Hospital, Saint Petersburg, Russia.
Summary:
Stroke was and remains one of the world’s leading medical and social problems. Nowadays we are watching permanent sometimes cardinal changes in view about etiology, pathogenetic mechanisms and therapy of patients with stroke. In this work there have been elucidated contemporary theoretical and practical aspects of stroke treatment and prophylaxis based on the results of multicenter clinical trials and experience of leading foreign and native specialists. Much attention is devoted to the pharmacotherapy of patients with stroke. It is showed that application of neuroprotective drugs is of great importance, among which antihypoxants with pleiotropic action play a crucial role (mexidol).
Keywords: stroke, therapy, prophylaxis, neuroprotection, antihypoxants, mexidol.
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.
Possibilities of antioxidant therapy for asthenia and cognitive deficit in elderly patients with chronic brain ischemia
Author:
S.N. DUMA.
Research Institute of Therapy, Siberian Branch, Russian Academy of Medical Sciences, Novosibirsk.
Summary:
Aim. To evaluate the effect of the antioxidant mexidol on the oxidant-antioxidant potential of low-density lipoprotein (LDL), asthenic and anxious symptoms, and cognitive function of neurodynamic type in elderly patients with chronic brain ischemia (CBI). Subjects and methods. Thirty women (mean age 66.7 years) with grade 1-2 dyscirculatory encephalopathy (DE) were examined. Trends for asthenic, anxious, and cognitive symptoms of neurodynamic type were estimated using the standard tests (MFI-20, Hamilton Anxiety Rating Scale, Schulte Tables, Wechsler test) on days 1, 15, and 60 of mexidol treatment (for 60 days). LDLs were isolated from blood by heparin precipitation. The baseline level of lipid peroxidation products was determined and the concentrations of fat-soluble antioxidants (α-tocopherol, retinol, β-carotene, and xanthins) were examined in the isolated LDLs on days 1 and 5 of the study. Results. A 60-day mexidol therapy cycle statistically significantly caused a reduction in asthenic and anxious symptoms in elderly patients with CBI and induced positive changes in the symptoms of cognitive neurodynamics. Assessing the specific features of the pharmacodynamics of the antioxidant mexidol used in the elderly patients for 15 days revealed a statistically significant positive effect on the oxidative potential of LDLs as a decreased predisposition to their antioxidative processes in vivo. The drug’s effect in elevating the levels of α-tocopherol and β-carotene was altered insignificantly (without statistically significant changes), which reflects the pharmacodynamic features of the drug in the elderly patients. Conclusion. The 60-day cycle of therapy with the antioxidant mexidol has a positive impact on asthenic and neurotic symptoms in the elderly patients with CBI. Mexidol is well tolerated and safe when used long.
Keywords: asthenia, anxiety, cognitive defect, chronic brain ischemia, elderly age, specific features of antioxidant therapy, mexidol.
Optimization of hypolipidemic therapy in patients with ischemic stroke and diabetes mellitus
Author:
L.A. SHCHEPANKEVICH, YU.A. NIKOLAEV, N.A. DOLGOVA.
Research Institute of Experimental and Clinical Medicine, Novosibirsk.
Summary:
Objectives. Evaluation of effectiveness of Mexidol in optimization of hypolipidemic therapy in ischemic stroke and diabetes mellitus patients. Material and methods. Authors analyzed the indicators of lipid status: total cholesterol, low-density lipoproteins, high density lipoproteins, triglycerides and concentration of platelet factor-4, β-tromboglobulin, von Willebrand factor in 68 patients with acute ischemic stroke and diabetes mellitus. Authors investigate the dynamics of these parameters (1st, 21st, 3-d and 6th month after onset stroke) depending on timing and dose of Mexidol. Results. Long time therapy of Mexidol may optimize of hypolipidemic therapy in ischemic stroke and diabetes mellitus patients.
Keywords: ischemic stroke, diabetes mellitus, comorbidity, lipids, hemostasis, mexidol.
Chronic cerebrovascular diseases associated with metabolic syndrome: new treatment approaches
Author:
M.M. TANASHYAN, O.V LAGODA, K.V. ANTONOVA.
Nevrology Research Center Russian Academy of Medical Sciences, Moscow.
Summary:
Metabolic syndrome is a risk factor for acute and chronic cerebrovascular diseases. The development of oxidative stress promotes the progression of cerebral ischemia and treatment of the biochemical disturbances is needed. Use of antioxidants in patients with cerebrovascular diseases and metabolic syndrome reduce such symptoms as insulin resistance, hyperglyceridemia, hyperglycemia. The authors present results of a clinical study of mexidol in 40 patients, aged from 50 to 70 years, with chronic cerebrovascular pathology. Perspectives of using this group of drugs as universal neuroprotectors are discussed.
Keywords: ischemic cerebrovascular diseases, antioxidant treatment, metabolic syndrome, mexidol.
Neurometabolic therapy in secondary prevention of stroke
Author:
V.V. KOVALCHUCK.
Semashko City Hospital №38, St. Petersburg.
Summary:
Objective. To study the efficacy of mexidol in secondary prevention of stroke. Material and methods: We analyzed 3400 patients with stroke which were stratified into 7 groups: patients with cryptogenic ischemic stroke (II), arterial hypertension, atrial fibrillation, metabolic syndrome, syndrome of sleep-induced obstructive apnea/hypnea, diabetes mellitus, vasculitis. The assessment of efficacy was based on the absence of repeated II within 5 years of therapy. Results. Mexidol reduced the frequency of repeated II both in patients without concomitant diseases and in those with arterial hypertension, syndrome of sleep-induced obstructive apnea/hypnea, vasculitis, diabetes mellitus, atrial fibrillation and metabolic syndrome. Conclusion. The reliable efficacy of mexidol in secondary prevention of stroke was found out.
Keywords: stroke, secondary prevention, mexidol.
Adaptogenic effects of mexidol in chronic cerebral ischemia
Author:
E.A. ANTIPENKO.
Summary:
The data on the effect of the succinate-containing antioxidant mexidol on the adaptation abilities of patients with chronic brain ischemia are presented. We studied 98 patients with discirculatory encephalopathy of I, II and III stages. A set of indices for psychoemotional status, functional state of the brain, autonomic status, nonspecific stability to hypoxia, adaptive reactions of the blood system and status of antioxidant defense have been used to evaluate adaptive abilities of the body. It has been shown that the introduction of the antioxidant in the treatment set strengthens the effects of basic treatment by increasing adaptive reserves of the body in stages I and II of disease that is related with the realization of reactions of urgent adaptation. The introduction of mexidol in the treatment set increases the frequency of favorable outcomes after one year of follow-up.
Keywords: brain ischemia, discirculatory encephalopathy, adaptation, adaptogenic effect, stress.
The use of succinates for the correction of metabolic disorders in the penumbra in patients with stroke
Author:
M.M. ODINAK, S.N. YANISHEVSKII, N.V. TSYGAN, S.YU. GOLOKHVASTOV, I.A. VOZNIUK, A.G. TRUFANOV.
Kirov Military Medical Academy, St. Petersburg.
Summary:
The aim of the study was to determine the quantitative content and correlation between metabolites in the core ischemic zone, the ischemic penumbra and the intact tissue of the opposite hemisphere in the acute stage of ischemic stroke using MR-spectroscopy. We studied 72 patients, including 37 patients (the main group) treated with the antioxidant mexidol (2-ethyl-6-methyl-3-hydroxypiridine succinate) in addition to standard therapy and 35 patients who received standard therapy only. The severity of stroke was assessed using the NIHSS. The Barthel index and Rankin scale were used to evaluate functional outcome in the 30th day, hydrogen MR-spectroscopy was used twice: in the first 24 h from disease onset and in the 5th day. Mexidol used in dose 500 mg intravenously during 14 days reduced significantly the content of lactate (p=0.002) and inositol (p=0.005) in the cells compared to the control group that enhanced the restoration of the balance between aerobic and anaerobic mechanisms of oxidation and positively influenced on the rehabilitation of patients. Positive correlations between the content of lactate in the ischemic penumbra and NIHSS scores (r=0.5786; p=0.049) and the negative correlation between the content of lactate in the ischemic penumbra and the degree of functional restoration assessed by the Barthel index (r= –0.6305; p=0.028) were found. These findings support the evidence for the interaction between the disturbance of glucose metabolism in conditions of hypoxia and the degree of nervous tissue damage.
Keywords: ischemic stroke, magnetic resonance spectroscopy, antioxidants, mexidol (2-ethyl-6-methyl-3-hydroxypiridine succinate).