Efficacy and safety of ethylmethylhydroxypyridine succinate in patients with ischemic stroke


1Research Centre for Examination of Medical Devices, Moscow, Russia;
2Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia;
3Pirogov Russian National Research Medical University, Moscow, Russia;
4Federal Scientific Center — All-Russian Scientific Research Institute of Experimental Veterinary Medicine named after K.I. Skryabin and Ya.R. Kovalenko, Moscow, Russia

Stroke is still the most significant problem of the modern medicine and the leading cause of mortality and morbidity. There is the great experience of neuroprotection in patients with stroke in the Russian Federation. In clinical practice it’s important to follow conditions, where neuroprotection will have maximum safety and effectiveness. The clinical trials of ethylmethylhydroxypyridine succinate (mexidol) in patients with acute ischemic stroke are described in the present review. Early management (in the first 6 hours) with mexidol significantly improve recovery dynamic and stroke outcome. Therapy with mexidol increases neurological recovery, improves vital activity and quality of life of patients with stroke. Furthermore, mexidol demonstrates high safety profile. Keywords: ischemic stroke, thrombolytic therapy, clinical trial, disability, antioxidant system, ethylmethylhydroxypyridine succinate, Mexidol.

The efficacy of ethylmethylhydroxypyridine succinate in patients with cerebrovascular pathology complicated with diabetes mellitus and metabolic syndrome

1Academy of Postgraduate Education under the Federal State Budgetary Unit «Federal Scientific and Clinical Center for Specialized Medical Assistance and Medical Technologies of the Federal Medical Biological Agency», Moscow, Russia;
2Belgorod State National Research University, Belgorod, Russia;
3Evdokimov Moscow State University of Medicine and Dentistry, Moscow, Russia

Arterial hypertension, diabetes mellitus, obesity and dyslipidemia continue to be the main risk factors for diseases of the circulatory system and the leading causes of mortality in the world, the combination of these diseases significantly increases the likelihood of the development and more rapid progression of cardiovascular and cerebrovascular pathology. Improving approaches to the diagnosis and treatment of these diseases is a priority problem in modern medicine. Currently, there is no universal drug that can influence all stages of pathological process in both cerebrovascular diseases and diabetes mellitus, and the problem of rational use of drugs in patients with comorbid pathology has not been completely resolved. A difficult clinical task includes not only the timely detection of the disease and the correct diagnosis, but also the choice of the safest and most effective medicine. A number of clinical studies have demonstrated the efficacy of mexidol in the treatment of this category of patients, which is determined by its complex, pleiotropic and multimodal mechanisms of action. Keywords: cerebrovascular diseases, diabetes mellitus, metabolic syndrome, antioxidant therapy, mexidol.

Effectiveness and safety of mexidol forte 250 in the sequential therapy in patients with chronic ischemia

1 Siberian State Medical University , Tomsk, Russia;
2 National Research Tomsk State University , Tomsk, Russia

Objective. To study of efficacy and safety of mexidol used as intravenous infusion for 14 days, followed by per os treatment with mexidol FORTE 250 for 60 days in patients with chronic brain ischemia (CHM) complicated with arterial hypertension and atherosclerosis. Material and methods. The mexidol group included 27 patients (24 women and 3 men) with CHM I—II gr and the combination of arterial hypertension and atherosclerosis who received intravenous infusions of mexidol (500 mg once daily) within 14 days, with the subsequent per os treatment with mexidol FORTE 250 in a daily dose of 750 mg (1 tablet 3 times a day) for 60 days. The comparison group consisted of 30 patients (22 women and 8 men) with CHM I—II gr, comparable in age, nature of risk factors and expression of neurological manifestations. Patients in both groups received basic medications to treat their risk factors. Motor activity (Tinetti test), cognitive functions (MoCa test), anxiety and depression (Hamilton anxiety and depression scale), clinical condition (General Clinical Impression scale) were assessed. Results and conclusion. Inclusion of mexidol (500 mg iv infusion once a day within 14 days with the subsequent oral administration of 750 mg (1 tablet 3 times a day) for 60 days) in standard therapy of arterial hypertension with atherosclerosis and chronic brain ischemia is expedient. The results show greater clinical efficacy and sufficient safety of such combination therapy. By the end of therapy (day 74), patients in the mexidol group have a reliable improvement in motor activity, cognitive function and psychoemotional sphere, as well as a decrease in fatigue and neurological manifestations compared with the comparison group. Keywords: chronic ischemia of a brain, mexidol, mexidol FORTE 250.

Efficacy and safety of Mexidol across age groups in the acute and early recovery stages of hemispheric ischemic stroke (results of additional sub-analysis of a randomized double blind multicenter placebo-controlled study, in parallel groups trial EPICA)



1Pirogov Russian National Research Medical University, Moscow, Russia;
2Russian Clinical and Research Center of Gerontology of Pirogov Russian National Research Medical University, Moscow, Russia;
3Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical (Sechenov University),
Moscow, Russia;
4Russian Medical Academy of Continuous Professional Education, Moscow, Russia

Aim. To evaluate the efficacy and safety of prolonged sequential therapy with mexidol in the acute and early recovery stages of hemispheric ischemic stroke (IS) across age groups according to the World Health Organization classification. Material and methods. The study is an additional analysis across age groups among patients participated in the randomized double blind multicenter placebo-controlled, in parallel groups trial EPICA. All subjects (62 men and 88 women) were subdivided into age groups: younger than 60 years, 60—65 years, 76—90 years. Additionally, all participants were divided into 2 populations: ITT (Intent to treat population, patients who received at least one treatment/placebo dose) and PP (Per protocol population, patients who received treatment per study protocol). Results of Modified Rankin scale (mRs) at the end of treatment period, Barthel index, Beck depression inventory, European Quality of Life Questionnaire were assessed. Results. The efficacy of mexidol assessed with all the scales did not differ depending on the age group. By the end of treatment, the mean mRS score was lower in the 76-90 years subgroup (in both populations), compared to placebo (p<0,001). The decrease in mean mRS score (Visit 1—5) was more prominent in patients aged 60—65 years (p=0,025), including patients with diabetes mellitus (DM). Patients aged 76—90 years and patients with DM, compared to placebo, had a decrease of the severity of cognitive-affective depression symptoms (p=0,049 and p=0,02) and an increase in patients without problems with everyday activities (p=0,007 and p=0,02). Patients with DM, compared to placebo, also had the higher levels of everyday activity (p=0,023) and quality of life (p=0,045). There were no statistically significant differences in the frequency of side-effects in patients of all groups. Conclusion. It is recommended to include mexidol in therapy of patients with IS in the acute and early rehabilitation stages in all age groups, including patients with DM. Keywords: ischemic stroke, mexidol, ethylmethylhydroxypyridine succinate, efficacy and safety, ischemic stroke, acute period, acute rehabilitation period, EPICA.

Efficacy and safety of ethylmethylhydroxypyridine succinate in patients with chronic cerebral ischemia

1Scientific Center for Examination of Medical Devices, Moscow, Russia;
2Sechenov First Moscow State Medical University, Moscow, Russia;
3Federal Scientific Center-all-Russian Research Skriabin and Kovalenko Institute of Experimental Veterinary Medicine the Russian Academy of Sciences, Moscow, Russia

Chronic cerebral ischemia (CCI) is a common cerebrovascular syndrome, the development of which is associated with a high risk of increasing cognitive, behavioral, and motor disorders, and the formation of a patient’s dependence on others. Timely start of treatment can slow down the course of the disease, make it more favorable. The review considers the possibility of using the domestic neuroprotector mexidol in patients with CCI. The results of a series of clinical studies on the use of ethylmethylhydroxypyridine succinate (mexidol) in patients with CCI are analyzed. The effectiveness of the drug in relieving cognitive, affective and motor disorders is noted. Information about the good tolerance of mexidol is presented. Keywords: chronic brain ischemia, cognitive disorders, affective disorders, ethylmethylhydroxypyridine succinate, Mexidol, treatment.

Possibilities of using Mexidol in the complex therapy of mental disorders

Kirov military medical Academy, St Petersburg, Russia

A review of the current literature on the possible use of mexidol (ethylmethylhydroxypyridine succinate) in the treatment of mental (including addictive) disorders is conducted. The possibility of its use to reduce negative psychopathological symptoms, neurocognitive deficit, manifestations of the antipsychotic syndrome (including its extrapyramidal disorders) in antipsychotic treatment of patients with schizophrenia spectrum disorders and insomnia disorders in the complex therapy of borderline mental disorders has been shown. The potential of mexidol in the treatment of addictive pathology, as well as the effects of intoxication caused by alcohol and other psychoactive (including narcotic) substances, deserves special attention.
Keywords: mental disorders, addictive pathology, Mexidol, treatment, complex therapy.

Effects of mexidol in patients with chronic brain ischemia and chronic heart failure (II-III functional class)

1People’ Friendship University of Russia, Moscow, Russia;
2Pavlov Ryazan State Medical University, Ryazan, Russia

Aim. To study the effect of mexidol on N-terminal pro B-type natriuretic peptide (NT-proBNP), markers of oxidative stress, inflammatory reaction and endothelial dysfunction in patients with chronic brain ischemia and chronic heart failure II-III NYHA functional class while 13 weeks of sequential intravenous and oral therapy with mexidol and standard therapy. Material and methods. Study included 44 patients with chronic brain ischemia and chronic heart failure II-III NYHA functional class with ejection fraction less 50%. Mean age: 65.5±11.8 years, 75% men. 21 patients of group mexidol plus standard therapy of chronic heart failure received mexidol at a dose of 1000 mg/day by intravenous infusion for 7 days followed by oral doses of 250 mg three times a day for twelve weeks, 23 patients received standard therapy. 34 patients completed the trial, in 10 patient the final visit was performed as telephone call due to epidemiologic situation. Concentration of N-terminal pro B-type natriuretic peptide (NT-proBNP), markers of oxidative stress (malonic dialdehyde (MDA), superoxide dismutase (SOD)), inflammatory reaction (C-reactive protein (CRP), tumor necrosis factor α (TNFα)), homocysteine and cystatin C were examined in blinded manner in all patients initially, on day 7 and week 13. Results. Statistically significant more prominent decrease of NT-proBNP, MDA, CRP and TNFα and increase of SOD by day 7 and week 13 were observed in patients treated with mexidol along with standard therapy in comparison with group treated with standard therapy. Conclusion. Mexidol added to standard therapy of patients with chronic brain ischemia and chronic heart failure II-III functional class decreases concentration of NT-proBNP, has proven antioxidant activity, decreases the degree of inflammatory reaction, slows down the increase of homocysteine, does not influence the kidney function (by measurement of cystatin C).
Key words: chronic brain ischemia, heart failure, oxidative stress, antioxidants, N-terminal pro B-type natriuretic peptide (NT-proBNP), malonic dialdehyde, superoxide dismutase, CRP, TNFα, ethyl-methyl-hydroxipyridin succinate, mexidol.

Antioxidants/antihypoxants: the missing puzzle piece in effective pathogenetic therapy for COVID-19

V.V.Zakusov Research Institute of Pharmacology, Moscow, Russian Federation

This review focuses on the specific characteristics of COVID-19 disease, which leads not only to respiratory impairments (bronchoalveolar epithelium does not retain oxygen, etc.), but also decreases the level of hemoglobin and its ability to transfer oxygen to the organs and tissues and increases the level of heme, resulting in anoxemia, hypoxia in all organs and tissues, and oxidative stress. Mexidol, a drug developed in Russia, is widely used in clinical practice, including the treatment of diseases accompanied by ischemia and hypoxia. Mexidol has antihypoxic and antioxidant effects, can treat mitochondrial respiratory dysfunction, thereby affecting the key processes in different cells of organs and tissues that develop due to hypoxia. Mexidol can be useful in the comprehensive therapy of patients with COVID-19. Key words: COVID-19, antioxidant, antihypoxant, hemoglobin, hypoxia, Mexidol, mitochondrial dysfunction, oxidative stress.

The role of oxidative stress in the development of vascular cognitive disorders

Pirogov Russian National Research Medical University, Moscow, Russia;
Federal Center of Brain Research and Neurotechnologies, Moscow, Russia

Vascular cognitive impairment (VCI) is one of the most serious problems of clinical neurology, being the second most common cause of dementia. VCI covers a range of disorders in which vascular factors cause or contribute to cognitive decline. Among the main risk factors for VCI are old age and vascular factors, which lead to endothelial dysfunction and damage, which, in turn, can cause neurovascular dysfunction, increased permeability of the blood-brain barrier, and microvascular thrombosis. Oxidative stress is one of the most important mechanisms for the development of VCI that indicates the need for the use of agents with antioxidant activity. One of these drugs is ethylmethylhydroxypyridine succinate (mexidol). Mexidol is a drug with marked antioxidant and antihypoxic activities. The clinical efficacy of mexidol in relation to VCI has been demonstrated in many studies. Keywords: chronic cerebrovascular insufficiency, oxidative stress, vascular cognitive impairment, endothelial dysfunction, mexidol.

Mexidol® and Mexidol® FORTE 250 in consecutive therapy of cognitive disorders in comorbid patients with joint pathology on the background of arterial hypertension and ischemic heart disease

Kuban State Medical University of the Ministry of Healthcare of Russia, Krasnodar

The aim of the study was to assess the efficacy, safety and possibility of correcting the neuropsychiatric manifestations of chronic cerebral ischemia (CCI) by Mexidol® on the background of arterial hypertension (AH), atherosclerosis (IHD), osteoarthritis (OA) or rheumatoid arthritis (RA). Material and methods. We examined 134 patients 45–75 years old with neurovizualized CCI, combined with hypertension, coronary artery disease, and joints pathology. Group 1 (observation) included 79 patients – 30 patients with RA (subgroup 1А) and 49 patients with OA of knee joints (subgroup 1B), who got Mexidol® in their complex therapy. Group 2 (control) consisted of 30 patients – 25 patients with RA (subgroup 2A) and patients with OA (subgroup 2B), who got basic therapy without Mexidol® addition. The dynamics of subjective and physical symptoms, values on the CGI, MoCA, MFI 20 scales, anxiety and depression scales of Hamilton and Tinnetti were estimated. Mexidol® was administered intravenously (500 mg per day) for 14 days, followed by oral administration of Mexidol® FORTE 250 by 250 mg 3 times/day for another 60 days. Results. On the background of constant standard complex therapy, an increasing improvement was revealed in all studied indexes in cases of additional use of Mexidol®. In control groups, the cognitive status did not change. The use of initiating intravenous therapy with Mexidol® increased the adherence of patients to long-term use of the drug. Conclusion. Locomotor dysfunctions in polymorbid patients are partially associated with CCI. The additional appointment of sequential infusion and tablet forms of Mexidol® significantly improves cognitive functions with the correction of walking stability, asthenic manifestations, and increases motivation for active life. Key words: chronic cerebral ischemia, Mexidol®, osteoarthritis, rheumatoid arthritis, arterial hypertension, ischemic heart disease.