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.


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.