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Preclinical experimental studies

The study of the influence of ethylmethylhydroxypyridine of succinate on the effectiveness of non -steroidal anti -inflammatory drugs with visceral and somatic pain in the experiment on mice and rats

Author:
E.A. Ivanova, A.G. Vasilchuk, A.I. Matyushkin, T.A. Voronin

FGBNU "Research Institute of Pharmacology named after V.V. Zakusova ”, Moscow, Russia

Place of publication:
a journal of neurology and psychiatry named after S.S. Korsakova, 2023, T. 123, No. 12

Summary:
Purpose of the study. To study the effect of ethyl-hydroxypyridine of the succinate (EMGPS) on the anti-Bolar effect of the non-election inhibitor of cyclooxygenase (COO) of the sodium diclofenac and selective chief-2 ethrioxib inhibitor on the models of acute visceral and somatic pain and evaluate the possibility of using EMGPS in combination with the inhibitors of the TSU for the reduction their doses with the preservation of anti -Bolar efficiency . Material and methods. The effect of EMGPS was studied with a single oral effect on anti-Bolar effects of non-steroidal anti-inflammatory drugs (NSAIDs): a non-melting inhibitor of the diclofenac sodium and selective TSOG-2-2 etrica inhibitor-on the models of acute visceral (vinegar croching test) and somatic pains (formalin tests the one Hyperalgesia with inflammation) in an experiment on mice and rats. Results. On the model of acute visceral pain in EMGPS mice (25–100 mg/kg) does not have a significant effect on its severity, but enhances the anti -Bolea effect of sodium diclofenac (0.5 mg/kg) and ethricoxib (1 mg/kg). In the formalin test in rats that simulates pain during operational cuts (injury), EMGPS (25 mg/kg) increases the severity of the anti -folly action of TSOG inhibitors (1 mg/kg) primarily due to a decrease in pain in the acute phase, due to the effect of formalin on afferent neurons . On the model of mechanical hyperalgesia in rats caused by exudative inflammation after injection of the Karraginan solution in the paw, the EMGPS enhances the effect of diclofenac to a greater extent than ethricoxib. Conclusion. The data obtained indicate the appropriateness of clinical study of the use of EMGPS in combination with NSAIDs for visceral and somatic pain in order to evaluate its ability to increase the therapeutic effect of NSAIDs. Keywords: ethylmethylhydroxypyridine succinate, non -steroidal anti -inflammatory drugs, visceral pain, somatic pain, mouse, rats.

Features and mechanism of the neuroprotective action of Mexidol with hemorrhagic stroke in the experiment

Author:
V.A. Kraneva

GU Nii Pharmacology named after V.V. Zakusov RAMS, Moscow

Place of publication:
Bulletin of experimental biology and medicine, 2006, Appendix 1

Summary:
on the model of experimentally caused intracerebral post -traumatic hematoma (hemorrhagic stroke), rats have established that the drug Mexidol is effective at a dose of 100 mg/kg (course - 7 days). The drug statistically reliably reduced the number of neurological disorders (paresis, manners), increased animal survival, improved the processes of learning and memory of rats with hemorrhagic stroke, as well as their motor activity. Key words: Mexidol, hemorrhagic stroke, neurological status, memory

The role of oxidative stress in acute experimental hemorrhagic stroke and therapeutic effects of Mexidol

Authors:
T.A. Voronina, V.A. Kraneva, N.N. Zolotov, S.O. Kotelnikova, E.A. Waldman

FGBNU "Research Institute of Pharmacology named after V.V. Zakusova ”, Moscow, Russia

Place of publication:
a journal of neurology and psychiatry named after S.S. Korsakova, 2022, T. 122, No. 8, Issue. 2

Summary:
Purpose of the study. The study of the role of oxidative stress in the development of disorders that occur with hemorrhagic stroke (GI), and the assessment of the influence of Mexidol on neurological and cognitive disorders with the analysis of the relationship of therapeutic effects of the drug with its antioxidant effect. Material and methods. The study was carried out on sexually mature out-and-aids weighing 260–280 g. The Gi model was created by destruction of brain tissue in the Capsula Interna with the introduction of blood damage to the place. On the 1st, 7th and 14th day after the modeling of GI in rats, death, neurological deficit (McGrow scale, a rotating rod, TVS), convulsive syndrome, violation of cognitive functions were recorded, a quantitative analysis of the indicators of oxidative stress with the assessment of TBK-active (thiobarbituric acid - TBK) products in blood plasma and homogenates of the cortex of the brain of rats. Mexidol was introduced after surgery in the first 3 days at a dose of 150 mg/kg intra-abdominal, then (from 4 to 14 days)-75 mg/kg inward. Results. Mexol in rats with GI significantly increases survival, reduces the severity of the neurological deficit on the McGROW scale (manners, paresis of 1-4 limbs, paralysis of the lower extremities, lateral position), eliminates convulsive attacks, restores violation of movement coordination (TVS) and improves training processes and improves training processes and improves learning processes and improves memory. Mexidol normalizes the concentrations of TBK-active products in the blood of animals and homogenes of the cortex of the brain of rats 1 and 7 days after the GI. Conclusion. The data obtained indicate the role of oxidative stress in the development of violations with the GI and the ability of Mexidol to weaken the neurological deficit, convulsive manifestations and cognitive disorders for GI, which limits the manifestations of oxidative stress. All this substantiates the significance of the use of Mexidol in patients with GI and determines the features of its therapeutic effects. Key words: hemorrhagic stroke, intracerebral hematoma, oxidative stress, Mexidol, neurological deficit, convulsions, cognitive disorders.

Heroprotective effects of ethylmethylhydroxypyridine of succinate in an experimental study

Author:
T.A. Voronin

FGBNU "Research Institute of Pharmacology named after V.V. Zakusova ”, Moscow, Russia

Place of publication:
a journal of neurology and psychiatry named after S.S. Korsakova, 2020, T. 120, No. 4

Summary:
Purpose of the study. Studying the influence of Mexidol on cognitive and motor functions disturbed during aging, the threshold of convulsive reaction, body weight and life expectancy in the old rat smams of the Vistar line. Material and methods. In a long experiment, a violation of cognitive functions (a test of conditional reflex of passive avoidance), motor disorders (tests of a rotating rod and pulling on the crossbar), a convulsive threshold (a test of subcutaneous administration of the pentilentetrazole), an animal mass and life expectancy were evaluated in a long experiment. Mexidol in the form of a 0.15% solution that replaced drinking water, rats received 2 courses of 2 months: at the age of 18-20 and 22-24 months. The dose of Mexidol consumed by the rat was 40–75 mg/kg/day. Results. Mexol in the old rat smams of the Vistar line with prolonged course use improves training, preservation and reproduction of a memorable trace in the test of conditional reflex of passive avoidance, increases the convulsive threshold and improves muscle tone and coordination of movements disturbed during aging, and increases life expectancy. The use of Mexidol allows us to prevent a significant increase in body weight, characteristic of aging. Conclusion. Mexidol reduces the severity of the cognitive and neurological deficiency that occurs during aging in the rats of the Vistar line, increases the threshold of convulsive reaction and increases life expectancy, which is determined by its ability to influence mitochondrioogenesis and antioxidant properties. Keywords: aging, Mexidol, life expectancy, memory violation, neurological deficit, convulsive threshold.

The role of free-radical oxidation, hypoxia and their correction in the pathogenesis of Covid-19

Authors:
A.V. Schulkin, A.A. Filimonova

FGBOU in the Ryazan State Medical University named after Acad. I.P. Pavlova "of the Ministry of Health of Russia

Place of publication:
therapy, No. 5 (39), 2020

Summary:
in the presented review, the pathogenesis of the coronavirus disease 2019 (Covid-19), features of the SARS-COV-2 virus are considered in detail. Given the great importance in the development of this infection of oxidative stress and hypoxia, it is advisable to use antioxidants and antihypoxants in the complex treatment of Covid-19, which may be useful and significantly improve the course of the disease. Key words : Covid-19, coronaviruses, oxidative stress, hypoxia.

The influence of Mexidol on the expression of the NRF2 transcription factor in the cortex of the large hemispheres of the brain with experimental ischemia

Authors:
E.N. Yakusheva, P.Yu. Mylnikov, I.V. Chernykh, A.V. Schulkin

FGBOU in the Ryazan State Medical University named after Acad. I.P. Pavlova "of the Ministry of Health of Russia, Ryazan, Russia

Place of publication:
Journal of Neurology and Psychiatry, 5, 2018

Summary:
Purpose of the study. To study the influence of the original domestic drug Mexidol on the expression of the transcription factor NRF2 in the cores of the cells of the frontal cerebral cortex with one -way occlusion of the general carotid artery. Material and methods. The work was done on 64 sexually mature rats of the Vistar line. The expression of NRF2 was determined by the immunohymic method. Results and conclusion. A single intra -Brushyne administration of Mexidol per 1 kg of body weight of the animal and its course oral administration per 1 kg of mass 3 times a day for 14 days did not affect the expression of the NRF2 factor. Unilateral occlusion of the general carotid artery increased the expression of NRF2 after 4 hours and on the 5th day after modeling occlusion. The oral administration of 100 mg of Mexidol per 1 kg of mass 3 times a day for 14 days before and after modeling ischemia increased the expression of NRF2 after 4 hours and on the 12th day compared to the norm indicators, as well as after 4 hours and on the 12th A day compared with the values ​​of the control of occlusion. Thus, it was established that Mexidol increases the expression of NRF2 in the frontal cortex of the rats of rats not in normal conditions, but with unilateral occlusion of the general carotid artery. Keywords: Mexidol, NRF2, ethylmethylhydroxypyridine succinate, ischemia, occlusion of the general carotid artery.

The influence of Mexidol on the expression of the factor induced by HIF-1α hypoxia in the cortex of the large hemispheres of the brain of rats with ischemia

Authors:
E.N. Yakusheva, P.Yu. Mylnikov, I.V. Chernykh, A.V. Schulkin

FGBOU in the Ryazan State Medical University named after Acad. I.P. Pavlova ", Ryazan, Russia

Place of publication:
Journal of Neurology and Psychiatry, 10, 2017

Summary:
Purpose of the study. To study the influence of Mexidol (ethylmethylhydroxypyridine of succinate) on the expression of the factor induced by hypoxia (HIF-1α), in the bark of the frontal lobe of the large hemispheres of the brain during its ischemia. Material and methods . The work was done on 64 sexually mature rats of the Vistar line. The expression of HIF-1α was determined immunohymic chemically. Results and discussion. It was established that a single intra-Brush administration of Mexidol at a dose of 120 mg/kg of mass and its course oral administration at a dose of 100 mg/kg of mass 3 times a day for 14 days does not affect the expression of the HIF-1α factor. Unilateral occlusion of the general carotid artery increases the expression of HIF-1α after 4 hours from the moment of occlusion. The oral introduction of Mexidol at a dose of 100 mg/kg of mass 3 times a day for 14 days before and after ischemia, increases the expression of HIF-1α after 4 and 12 hours compared with the norms of the norm on the 5th day compared to the values ​​of occlusion control. Thus, it was established that Mexidol increases the expression of HIF-1α in the frontal cortex of the rats of rats not in normal conditions, but with unilateral occlusion of the general carotid artery.

Geronto -informational analysis of the properties of the Mexidol molecule

Authors:
O.A. Gromova 1.2 , I.Yu. Torshin 2 , L.E. Fedotova 1

1 FSBEI in the "Ivanovo State Medical Academy", Ivanovo;
2 FSBI "Federal Research Center" Informatics and Management "of the Russian Academy of Sciences, Moscow

Place of publication:
neurology, neuropsychiatry, psychosomatics, 2017, No. 9

Summary:
The purpose of the study is a comprehensive assessment by means of pharmacinformation profiling of all possible effects of mexidol molecules, alfoseta choline, piracetam, glycine, semax in accordance with anatomical and therapy-chemical classification. Material and methods. Hemoreactomic, pharmacinformation and geronto -informational analyzes of the properties of molecules are based on a chemorectic methodology. For chemoreactic analysis, information from the databases Pubchem, HMDB and String was used; For pharmacinformation analysis - information from the international classification of ATX and a combined data selection from the TTD (Therapeutic Target Database), Supertarget, Matador (Manually Annoted Targets and Drugs Online Resource) and PDTD (Potential Drugs Database); For gerontoinformation analysis, data on the heroroprotective action of individual substances from the Pubchem database and the literature on Heroproteus from the Pubmed base, collected through the system of artificial intelligence. Results and discussion. Mexidol is characterized by a maximum set of positive effects (a drug for the treatment of central nervous system diseases, cardiovascular pathology, metabolic disorders, which has anti-inflammatory and anti-infectious properties, etc.). Mexidol and glycine predict the smallest frequencies of such side effects as itching, constipation, paresthesia, vomiting, etc. Geronto -information assessments of changes in the life expectancy of model organisms showed that Mexidol helps to increase the average life expectancy of C. Elegans (by 22.7 ± 10%) , Drosophiles (by 14.4 ± 15%) and mice (by 14.6 ± 3%, control drugs - not more than 6.1%). Conclusion. The results of the study indicate the high potential of Mexidol for use as a hero of the Heroprotector.

Comparative chemoreactic analysis of Mexidol

Authors:
I.Yu. Torshin 1 , O.A. Gromova 2 , I.S. Sardaryan 3 , L.E. Fedotova 3

1 FSBEI in Moscow Physics and Technology Institute, Dolgoprudny, Russia;
2 FSBEI in the "Ivanovo State Medical Academy" of the Ministry of Health of Russia, Ivanovo, Russia;
3 FSBEI in St. Petersburg State Pediatric University of the Ministry of Health of Russia, St. Petersburg, Russia

Place of publication:
a journal of neurology and psychiatry, 1, 2017; Ext. 2

Summary:
Purpose of the study. Comparative chemorectic analysis of the Mexidol molecule (ethylmethylhydroxypyridine succinate) with control molecules (alpha alphascerate, piracetam, glycine, semax). Material and methods . Comparisons of the chemical structure of Mexidol with molecules in the database of human metabolism and molecules in the databases of drugs. More than 40,000 compounds given in the HMDB (Human Metabolome Database) were used as a human metabolism. Results and conclusion. Hemorestom analysis showed that Mexidol can be an agonist of acetylcholine and gamut-a receptors; anti -inflammatory agent, the effects of which occur due to inhibiting the synthesis of pro -inflammatory prostaglandins; neuroprotective agent with neurotrophic properties; coagulation inhibitor; sugar -lowering and hyalipidemic agents. Mexol molecules are distinguished by a more pronounced safety profile (less impact on serotonin, dopamine and adrenergic receptors, a lower degree of interaction with potassium potatoes, Mao enzymes and p450 cytochromas). The results of modeling allow at the molecular level to clarify the mechanism of action of the Mexidol molecule.

The distribution of Mexidol in the structures of the brain, its cellular elements and subcellular fractions

Authors:
A.V. Schulkin, E.N. Yakusheva, I.V. Black

Ryazan State Medical University named after Academician I.P. Pavlova

Place of publication:
Journal of Neurology and Psychiatry, 8, 2014

Summary:
The purpose of the study is to study the penetration of Mexidol through the hematoencephalic barrier (GEB) in different parts of the brain and mitochondria of cells. Material and methods. Used the drug Mexol LLC NPK Pharmasoft (Russia). They studied the penetration of large hemispheres, cerebellum, thalamus and oblong brain into the fabric and the distribution between mitochondrial and cytoplasmic fractions of nerve cells. The concentration of Mexidol in the blood plasma and brain tissue was analyzed by the method of highly effective liquid chromatography. Results and conclusion. It was established that Mexidol penetrates through the GEB into different parts of the brain of rats. Its greatest concentration is determined in the fabric of the bark of large hemispheres. Inside the nerve cells of Mexidol is found both in the cytoplasmic and mitochondrial fractions. Keywords: Mexidol, Pharmacokinetics, Hematoencephalic Barrier, Big Hses, Mozheschok, Thalamus, Minuted Brain, Mitochondria, Highly Effective Liquid Chromatography.

Mexidol and hepatitis: the results in the experiment and prospects in the clinic

Author:
N.F. Farashchuk

GOU VPO Smolensk State Medical Academy

Place of publication:
Bulletin of experimental biology and medicine, 2006, Appendix 1

Summary:
the influence of Mexidol in different doses in the dynamics of the development of experimental toxic hepatitis according to indicators of hydration and free radical oxidation in the blood and liver tissue has been studied. A positive and dose-dependent effect of Mexidol on the studied physicochemical processes in the blood and liver tissue in the experiment is established, its use in patients with diffusion liver diseases is theoretically substantiated. Key words: hepatology, intoxication, free radical processes, Mexidol.

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