Efficacy and safety of ethylmethylhydroxypyridine succinate in patients with chronic cerebral ischemia
Author:
M.V. ZHURAVLEVA1,2, A.B. PROKOFIEV1,2, S.YU. SEREBROVA1,2, N.S. VASYUKOVA3, E.YU. DEMCHENKOVA1, V.V. ARKHIPOV1
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
Summary:
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
Author:
V.K. SHAMREY, E.S. KURASOV, V.V. NECHIPORENKO, A.I. KOLCHEV, N.V. TSYGAN
Kirov military medical Academy, St Petersburg, Russia
Summary:
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)
Author:
A.V. SHCHULKIN2, E.R. KAZAKHMEDOV1, S.A. GALOCHKIN1, V.V. TOLKACHEVA1, Zh.D. KOBALAVA1
1People’ Friendship University of Russia, Moscow, Russia;
2Pavlov Ryazan State Medical University, Ryazan, Russia
Summary:
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
Author:
T.A. VORONINA
V.V.Zakusov Research Institute of Pharmacology, Moscow, Russian Federation
Summary:
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
Author:
A.N. BOGOLEPOVA
Pirogov Russian National Research Medical University, Moscow, Russia;
Federal Center of Brain Research and Neurotechnologies, Moscow, Russia
Summary:
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
Author:
L.N. ELISEEVA, S.V. KARTASHOVA
Kuban State Medical University of the Ministry of Healthcare of Russia, Krasnodar
Summary:
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.
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
Author:
L.N. ELISEEVA, S.V. KARTASHOVA
Kuban State Medical University of the Ministry of Healthcare of Russia, Krasnodar
Summary:
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.
The efficacy and safety of Mexidol and Mexidol Forte 250 in patients with chronic cerebral ischemia
Author:
Yu.V. ABRAMENKO
Tver State Medical University, Tver, Russia
Summary:
Objective. To study the efficacy and safety of mexidol’s intravenous injections (500 mg once a day) for 14 days, followed by oral administration of mexidol FORTE 250 at a dose of 250 mg (1 tablet) 3 times a day for 60 days, in treatment of chronic cerebral ischemia (CCI) in patients with hypertension and atherosclerosis of the brachiocephalic arteries. Material and methods. The observation program included 60 patients with an established diagnosis of CCI confirmed by neuroimaging methods. Patients of the main group (n=26) received mexidol along with basic therapy, patients of the comparison group (n=26) received only basic therapy. Results and conclusion. The results of the experience show the high efficacy and safety of sequential therapy (parenteral therapy followed by tablets of mexidol FORTE 250). The treatment improves emotional and cognitive status, decreases static-motor disorders and severity of subjective neurological symptoms. High adherence of patients to the therapy is shown.
Keywords: chronic cerebral ischemia, arterial hypertension, atherosclerosis of the brachiocephalic arteries, mexidol, static-motor
disorders, cognitive impairment.
Geroprotective effects of ethylmethylhydroxypyridine succinate in an experimental study
Author:
T.A. VORONINA
FSBI «Zakusov Institute of Pharmacology», Moscow
Summary:
Objective. To study an effect of mexidol on the life expectancy, weight, seizure response thresholds, and impaired cognitive and
motor functions during aging in male Wistar rats. Material and methods. In a long-term experiment, male Wistar rats, aged 3—26 months, were assessed for impaired cognitive functions (passive avoidance conditioned reflex test), convulsive threshold (test with pentylenetetrazole), motor deficits (tests of rotating rod and pulling on the crossbar), and life expectancy. The rats received mexidol in the form of 0,15% solution, which replaced drinking water, during two 2 month courses at the age of 18—20 and 22—24 month. A dose of mexidol consumed by the rat was 40-75 mg/kg/day. Results. In old male Wistar rats, the long-term treatment with mexidol increases the life expectancy, improves learning, preservation and reproduction of the memory trace in the passive avoidance conditioned reflex test, increases the convulsive threshold and improves muscle tone and coordination of movements that are impaired during aging. Conclusion. Mexidol increases the threshold of convulsive reaction, restores cognitive and neurological deficits that occur during aging in male Wistar rats and increases the by its ability to influence mitochondriogenesis and antioxidant properties.
Keywords: aging, mexidol, life expectancy, memory impairment, neurological deficit, convulsive threshold.
The effect of Mexidol on cerebral mitochondriogenesis at a young age and during aging
Author:
YU.I. KIROVA1, F.M. SHAKOVA1, E.L. GERMANOVA1, G.A. ROMANOVA1, T.A. VORONINA2
1 Institute of General Pathology and Pathophysiology, Moscow, Russia;
2 Zakusov Research Institute of Pharmacology, Moscow, Russia
Summary:
Objective. To study the ability of mexidol to induce cerebral mitochondriogenesis in the brain of young and aging rats. Material and methods. Expression level of marker proteins of cerebral mitochondriogenesis was evaluated during treatment with mexidol (20, 40, 100 mg/kg; 20 days; intraperitoneally) in the cerebral cortex of young (3 month) and aging (6, 9, 12, and 15 month) outbred male rats, using the Western blot analysis. Results. It has been shown for the first time that the course injections of mexidol in doses of 40 and 100 mg/kg is accompanied by dose-dependent induction of the succinate receptor SUCNR1 and protein markers of mitochondrial biogenesis: transcription coactivator PGC-1α, transcription factors (NRF1, TFAM), catalytic subunits of respiratory enzymes (NDUV2, NDUV2,cytb, COX2) and ATP synthase (ATP5A) in the cerebral cortex of young and aging outbred male rats. Mexidol-dependent overexpression of subunits of mitochondrial enzymes and PGC-1α is observed only with the course of the drug. Conclusion. The results indicate the ability of mexidol to induce cerebral mitochondriogenesis and eliminate mitochondrial dysfunction in young and aging animals and, thus, exert an effect on one of the key pathogenetic links of the development of disorders in aging and neurodegenerative diseases.
Keywords: aging, mitochondrial dysfunction, mexidol, succinate receptor, cerebral mitochondriogenesis, transcriptional coactivator PGC-1α, respiratory enzyme subunits, rats, Western blot analysis.