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.


Results of a Randomized, Double-Blind, Multicenter, Placebo-Controlled, Parallel-Group Study of the Efficacy and Safety of Mexidol in Prolonged Sequential Therapy of Patients in the Acute and Early Recovery Stages of Hemispheric Stroke (the EPICA study)

Author:
L. V. Stakhovskaya1, N. A. Shamalov1, D. R. Khasanova2, E. V. Mel’nikova3, A. S. Agaf’ina4, K. V. Golikov5, E. I. Bogdanov6, A. A. Yakupova6, L. V. Roshkovskaya7, L. V. Lukinykh8, T. M. Lokshtanova9, I. E. Poverennova10, and L. A. Shchepankevich11

1 Research Institute of Cerebrovascular Pathology and Stroke, Pirogov Russian National Research Medical University, Russian Ministry of Health, Moscow, Russia; e-mail: lstakh@mail.ru.

2 Interregional Clinical Diagnostic Center, Kazan, Russia.

3 St. Petersburg City Clinical Hospital No. 26, St. Petersburg, Russia.

4 St. Petersburg City Clinical Hospital No. 40 of the Resort Administrative District, St. Petersburg, Russia.

5 St. Petersburg City General Hospital No. 2, St. Petersburg, Russia.

6 Kazan Sate Medical University, Russian Ministry of Health, Kazan, Russia.

7 Nikolaevskaya Hospital, St. Petersburg, Russia.

8 Vsevolzhsk Clinical Interregional Hospital, Leningradskaya Oblast, Russia.

9 Pirogov City Clinical Hospital No. 1, Samara, Russia.

10 Seredavin Samara Regional Clinical Hospital, Samara, Russia.

11 Research Institute of Experimental and Clinical Medicine, Novosibirsk, Russia.

Summary:
Objectives. To assess the effi cacy and safety of prolonged sequential therapy with Mexidol in patients with hemispheric ischemic stroke (IS) in the acute and early recovery phases. Materials and methods. A randomized, double-blind, multicenter, placebo-controlled, parallel-group study included 151 patients (62 men and 89 women) was performed in which 150 patients (62 men and 88 women) aged 40–79 years were randomized. Simple randomization was used to defi ne two groups: patients of group 1 received Mexidol therapy at a dose of 500 mg/day by intravenous infusion for 10 days followed by oral doses of 1 tablet (125 mg) three times a day for eight weeks. Patients of group 2 received placebo by the same protocol. The duration of involvement in the trial was 67–71 days. Results. At the end of treatment, mean scores on the modified Rankin scale (mRS) were lower in group 1 than group 2 (p = 0.04). Decreases in mean mRS scores (at visits 1–5) were more marked in group 1 (p = 0.023). The proportion of patients achieving recovery corresponding to 0–2 points on the mRS (at visit 5) was signifi cantly greater in group 1 (p = 0.039). Testing on the National Institutes of Health Stroke Scale at visit 5 gave a signifi cantly lower score in group 1 (p = 0.035). Decreases in scores on the National Institutes of Health Stroke Scale at the end of treatment relative to the baseline level in patients with diabetes mellitus were more marked in group 1 (p = 0.038). In group 1, the total population and the subpopulation of patients with diabetes mellitus showed more marked improvements in quality of life, which was apparent by visit 2. The proportion of patients without diffi culty mobilizing was signifi cantly greater in group 1 (p = 0.022). There were no signifi cant differences in the frequencies of adverse events in patients of the two groups. Conclusions. Use of Mexidol in the acute and early recovery phases of IS is recommended. Keywords: acute cerebrovascular accident, Mexidol, ethylmethylhydroxypyridine succinate, effi cacy and safety, ischemic stroke, acute phase, early recovery phase, EPICA.


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 efficacy and safety of ethyl methyl hydroxypyridine succinate used as part of sequential therapy in patients with chronic cerebral ischemia

Author:
V.V. BURDAKOV, D.V. KRASNYKH
Orenburg State Medical University, Ministry of Health of Russia, Orenburg, Russia

Summary:
Objective: to investigate the efficacy and safety of Mexidol® FORTE 250 in patients with chronic cerebral ischemia (CCI) in the presence of hypertension and atherosclerosis. Patients and methods. The investigation enrolled 20 patients aged 45 to 75 years with CCI in the presence of hypertension and atherosclerosis, who received intravenous Mexidol® administered dropwise at a dose of 500 mg once a day for 14 days, followed by oral Mexidol® FORTE 250 mg thrice a day for 60 days (a study group). A control group consisted of 14 patients with CCI in the presence of hypertension concurrent with atherosclerosis, who were prescribed combination therapy for CCI without using these drugs. The patients were examined before and at 14 and 60 days of treatment. The investigators studied subjective complaints, neurological symptoms, and the indicators of the Tinetti Performance Oriented Mobility Assessment in Elderly Patients; the Montreal Cognitive Assessment (MoCA); the Hamilton Anxiety Rating Scale (HARS); asthenia rating scales (Multidimensional Fatigue Inventory, MFI-20); and the Clinical Global Impression (CGI) scale over time. Results and discussion. Therapy with Mexidol® in patients with CCI in the presence of hypertension and atherosclerosis was found to be accompanied by positive changes in the asthenia rating scale MFI-20, cognitive functions assessed by MoCA, as well as Tinetti movement coordination. No significant differences in these indicators were noted in patients of the control group. Combination treatment for CCI with Mexidol® and Mexidol® FORTE 250 as a sequential therapy was twice more effective than that without using these drugs, as shown by the scales as a whole and it was up to 10 times greater for individual scale parameters. Conclusion. The study of Mexidol® FORTE 250 as part of the sequential therapy, which was used according to the above regimen, indicates its clinical efficacy and safety in patients with CCI.
Keywords: chronic cerebral ischemia, cognitive and motor functions, asthenic and anxiety-depressive disorders, Mexidol® FORTE 250.


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.


The efficacy of ethylmethylhydroxypyridine in the rehabilitation treatment of poststroke patients

Author:
O.V. M.V. ZHURAVLEVA1,2, A.B. PROKOFIEV1,2, V.V. ARKHIPOV1, S.YU. SEREBROVA1,2, G.I. GORODETSKAY1,2, O.A. DEMIDOVA1

1 Research center for examination of medical devices, Moscow, Russia

2 Sechenov First Moscow state medical University (Sechenov University), Moscow, Russia

Summary:
The analysis of the clinical efficacy and safety of ethylmethylhydroxypyridine succinate (mexidol) in the complex of rehabilitation measures in patients after ischemic stroke (IS) shows that course treatment with mexidol improves the recovery of neurological functions, decreases neurological deficit, cognitive disorders, including memory impairment, and manifestations of asthenic syndrome, increases the level of social adaptation and improves the psycho-emotional state of patients, reduces spasticity, increases motor and speech activity, praxis, reliably eliminates the ignoring syndrome. There is a decrease in the level of total cholesterol and low-density b-lipoproteins in the blood, and decrease in the severity of hypercoagulation. The results of the studies have convincingly shown the efficacy of mexidol at all stages of rehabilitation treatment of patients with IS.
Keywords: ethylmethylhydroxypyridine succinate, mexidol, rehabilitation, recovery, stroke.


Efficacy and safety of the drug Mexidol forte 250 as part of long-term sequential therapy in patients with carotid stroke

Author:
I.A. STRELNIKOVA1, A.A. SVETKINA1,2, O.V. ANDROFAGINA1

1 Samara Regional Clinical Hospital named after V.D. Seredavina, Samara, Russia;

2 Samara State Medical University, Samara, Russia

Summary:
Objective. To evaluate an effect of long-term sequential therapy with mexidol and mexidol forte on the functional outcome of patients with carotid ischemic stroke. Material and methods. The study included 50 patients with newly developed carotid stroke, hospitalized in the stroke unit on the first day from the onset of the disease. Patients of the main group (n=25) received mexidol in a dose of 500 mg intravenously once a day for 14 days, then mexidol forte 250 in tabs 250 mg 3 times a day for 60 days. Patients of the comparison group (n=25) received standard basic therapy. The significance of intergroup differences was assessed using the Mann—Whitney test, Fisher’s exact test, and relative risk (OR) calculation. Differences were considered significant at a level of p<0,05. Results. After 14 days of therapy, both groups of patients showed a positive trend compared to baseline. At the same time, patients of the mexidol group had a higher MoCA score (U=173,5, p=0,006), a lower score when performing tasks on dynamic praxis (U=214,0, p=0,028) and optical spatial disturbances (U=170,5, p=0,003), better memorization strength (181,5, p = 0,006) and better performance on abstraction MOCA subtest (U=200,5, p=0,014). By the 74th day, the absence of moderate cognitive impairment (MoCA> 26 points) was diagnosed in 17 patients (68%) of the main group and 14 patients (56%) of the comparison group. No significant differences were found. Moreover, patients of the main group had a significantly lower NIHSS score (U=124,0, p<0,001) and a lower degree of disability: a total mRS score 0—2 was achieved in 19 (76%) patients of the main group and only in 12 (48%) patients of the comparison group (OR=3,34, F=0,07, p<0,05). Also, patients receiving long-term sequential therapy with mexidol and mexidol forte 250 had milder spatial disorders than patients of the comparison group. Conclusion. Consecutive treatment with mexidol and mexidol forte 250 in the acute and early recovery periods of ischemic stroke positively affects the regression of local neurological symptoms, increases the likelihood of achieving independence in everyday life by 3,34 times, and reduces the severity of optical-spatial, neurodynamic and memory impairments.
Keywords: ischemic stroke, mexidol, mexidol forte 250, cognitive impairment, functional outcome.


Possibility of application Mexidol for the treatment of patients suffering from sensorineural hearing loss and cerebrovascular insufficiency

Author:
N.L. KUNELSKAYA1, 2, YU.V. LEVINA1, 2, E.S. YANYUSHKINA1, D.S. OGORODNIKOV1, 2, E.V. LARIONOVA1
1 L.I. Sverzhevskiy Research Institute of Clinical Otorhinolaryngology, Moscow Health Department, Moscow, Russia, 117152;
2 Department of Otorhinolaryngology N.I.Pirogov Russian National Research Medical University (RNRMU), Moscow, Russia,117997

Summary:
Sensorineural hearing loss can develop as a consequence of vascular pathology. The etiology and pathogenesis of chronic sensorineural hearing loss allow us to consider promising the use of neuroprotective drugs in the treatment regimen that can activate the function of the neural structures of the auditory pathway. Ethylmethylhydroxypyridine succinate, having complex pharmacological capabilities and a wide range of effects realized at the neural and vascular levels can be used in the treatment of hearing impairment and speech intelligibility.
Keywords: hearing loss, sensorineural hearing loss, rehabilitation of auditory function, Ethylmethylhydroxypyridine succinate.