The targeted search, development and implementation of new highly effective drugs with minimal side effects are an urgent task of modern pharmacology, in particular sports pharmacology. Such drugs include vasoactive agents, nootropics, antihypoxants and antioxidants, as well as drugs with neurotrophic and neuromodulatory effects. One of these drugs is mildronate (meldonium dihydrate), which in its structure is a synthetic analogue of the precursor of carnitine biosynthesis - gamma-butyrobetaine. Like carnitine, it is involved in the energy metabolism of cells and thereby prevents the activation of glycolysis reactions, which dominate under conditions of tissue hypoxia, affecting the oxidation of free fatty acids [1]. Side effects of mildronate include dyspepsia, agitation, tachycardia, changes in blood pressure, and skin itching. Contraindications to its use are hypersensitivity and organic lesions of the central nervous system. In addition, it is believed that patients with chronic liver and kidney diseases should use caution during long-term use of mildronate.
The domestic drug Mexidol (2-ethyl-6-methyl-3-hydroxypyridine succinate) has a multicomponent spectrum of pharmacological effects and a multifactorial mechanism of action. Among them, the most important are its antioxidant, antihypoxic, membranotropic effects, the ability to modulate the functioning of receptors and membrane-bound enzymes and restore neurotransmitter balance [2, 3]. The mechanism of the antihypoxic action of Mexidol is associated primarily with its specific effect on energy metabolism, which is due to the succinate included in its composition, which, under hypoxic conditions, entering the intracellular space, is capable of being oxidized by the respiratory chain. Mexidol is an antihypoxant with direct energizing action, the effect of which is associated with the influence on endogenous respiration of mitochondria and activation of their energy-synthesizing function. The effect of Mexidol is due to an increase in compensatory metabolic flows that supply energy substrates to the respiratory chain, in this case succinate [3, 4]. The antioxidant and membrane-protective effects of Mexidol limit the destruction of lipid peroxidation products and contribute to the stabilization of cell membranes, the preservation of their ordered structural and functional organization, necessary for the functioning of membrane-bound receptor complexes, enzymes and ion channels. Due to the presence of succinate in the structure of the drug, Mexidol improves the energy balance of the cell and restores, under conditions of acute oxygen deficiency, the impaired process of oxidative phosphorylation associated with the limitation of the NADH oxidase pathway [2, 3].
Mexidol has a pronounced anxiolytic effect. It is able to eliminate fear, anxiety, tension, restlessness; has an anti-stress effect, for example, during stress in a new environment, anxiety and fear, and anticipation of pain [3]. Analysis of the mechanism of implementation of the anxiolytic effect of Mexidol showed that the drug does not have a direct affinity for benzodiazepine and GABA receptors, but has a modifying effect on them, enhancing their ability to bind [5, 6]. These effects are complemented by Mexidol’s unique ability to increase the body’s resistance to various extreme factors, such as stress, conflict situations, electric shock, physical activity, hypoxia, lack of sleep, and various intoxications [3, 7].
In addition, the spectrum of pharmacological activity of Mexidol shows anti-ischemic and neuroprotective effects, the ability to improve and stabilize brain metabolism and cerebral blood supply, correct disorders of the regulatory and microcirculatory systems, improve the rheological properties of blood, inhibit platelet aggregation, reduce total cholesterol levels, have an anti-atherosclerotic effect and cause activation of the immune system [3, 5, 7]. Along with this, the drug has virtually no side effects of traditional neuropsychotropic drugs [2].
Thus, thanks to its mechanism of action and a wide range of pharmacological effects, Mexidol influences not only the main links in the pathogenesis of various diseases associated with free radical oxidation processes, but is also capable of correcting oxygen-dependent pathological conditions in acute and chronic fatigue and other pathological conditions in sports, especially thereby increasing physical performance and reducing fatigue.
The purpose of the study was to study the effect of Mexidol in comparison with mildronate on the physical performance of animals in an experiment with a single and subchronic administration.
Indications for use
Mexidol is recommended by doctors for use in the following cases:
- mild traumatic brain injuries and their consequences,
- consequences of cerebral circulatory disorders,
- encephalopathy of various origins,
- influence of stress (extreme) factors,
- prevention of the occurrence of somatic diseases provoked by extreme stress and factors,
- flu therapy,
- relief of hangover syndrome,
- coronary heart disease,
- anxious moods against the background of neurosis-like and neurotic conditions,
- mild cognitive disorders of atherosclerotic origin, etc.
Doctors recommend using Mildronate to cure myocardial dystrophy, and also in the presence of the following diseases and conditions of the body:
- chronic heart failure,
- cardiomyopathy in dyshormonal disorders,
- coronary heart disease and its complex therapy,
- hangover syndrome due to chronic alcoholism,
- physical and mental stress,
- noise in ears,
- memory impairment,
- flu, colds,
- vestibulo-atactic syndrome, which is accompanied by flashing “flies” before the eyes,
- decreased performance,
- complex therapy of cerebrovascular insufficiency, stroke and other chronic and acute disorders of the cerebral circulatory process, etc.
Pharmadynamics and therapeutic effects
There is an opinion that Mexidol and Mildronate have the same effect, however, it is not entirely true. Despite the fact that the drugs have many of the same effects, the difference between them is quite significant.
The presence of the active ingredient in Mildronate, meldonium, gives the drug the following effects:
- Angioprotective. Suppresses the production of inflammatory mediators. Normalizes the permeability of the walls of blood vessels, increasing their tone. Helps improve blood microcirculation.
- Angianal. Helps eliminate coronary insufficiency and actively fights angina attacks. Thanks to the drug, oxygen delivery to the heart muscle increases.
- Antihypoxic. Increases the tolerance of the body as a whole or its individual tissues to a lack of oxygen caused by various reasons.
- Cardioprotective. Corrects and restores myocardial activity.
Mildronate promotes:
- improving cellular metabolism;
- normalization of blood microcirculation by eliminating vasoconstriction;
- slowing down the process of necrosis;
- reducing the period of recovery of the body after surgical interventions or illnesses;
- improving myocardial contractility;
- increasing the body's resistance to physical and mental stress;
- increasing immunity at the cellular level;
- elimination of some eye diseases.
Mexidol has the following effects:
- Antioxidant. Neutralization of free radicals leads to increased immunity, normalization of the functional abilities of all organs, prevention of aging, etc.
- Membrane stabilizing. Helps restore and increase the stability of cell membranes, their structure and properties.
- 3Antihypoxic. Participates in supplying cells with oxygen when it is lacking.
- Nootropic. Normalizes nutrition and blood circulation in the brain. This effect improves higher mental properties (memory, perception, speech, thinking). In addition, the drug protects the gray matter of the brain from overload and oxygen deficiency.
- Anticonvulsant. Eliminates and prevents the appearance of involuntary muscle contractions.
- Anxiolytic. Helps cope with feelings of anxiety, restlessness, and normalize the emotional background.
Mexidol also reduces the toxicity of antifungal agents and antibiotics when used.
The use of Mexidol leads to:
- to increase the level of dopamine in the brain, normalize metabolism in the organ and improve cerebral blood supply;
- improving blood microcirculation, its rheological parameters and reducing red blood cell aggregation;
- reduction of low-density lipoprotein levels;
- stabilization of cell membranes;
- normalization of metabolism and blood flow in ischemic areas of the heart muscle;
- reducing the area affected by necrosis;
- restoration and improvement of cardiac electrical activity and organ contractility;
- restoration of higher mental properties of the brain;
- improving the mental state after suffering stressful conditions;
- elimination of manifestations of intoxication (neurological and neurotoxic) after prolonged consumption of alcoholic beverages.
Both drugs are used not only to eliminate unpleasant symptoms, but also during sports to increase the body's endurance and recovery after sports competitions.
How are the drugs different?
Mildronate and Mexidol are different drugs that differ both in indications and in their effect and composition.
Characteristics of active ingredients
The active ingredient of Mexidol is ethylmethylhydroxypyridine succinate. Mildronate is a drug based on meldonium.
What is better - Mexidol or Mildronate?
It can be difficult to make a normal comparison between the 2 medications in question due to their differing actions. Mexidol is more effective for disorders in the blood circulation of the brain and heart diseases, which are accompanied by increased emotional and psychological stress.
General information about Mildronate
Mildronate is used in the treatment of various diseases to improve intracellular metabolism, to increase vitality and has a general strengthening effect. The active ingredient is meldonium.
Due to its cardioprotective properties, it is used in the treatment of heart diseases associated with ischemia (reduces necrotic zones during myocardial infarction, reduces the frequency and duration of angina attacks).
Effects of the drug Mildronate on the body
The drug is able to improve blood supply to the brain, which leads to improved cognitive functions, increased performance, and shortens the recovery period after strokes. It fights hypoxia at the cellular level - this allows it to be used in sports to restore the strength of athletes between performances and during training.
This drug is produced by a Latvian pharmacological company in various forms for ease of use:
- capsules;
- syrup;
- solution for injection (intramuscular, intravenous and parabulbar).
Mildronate has a preventive effect on the course of the disease, improving the course of the disease, alleviating the patient's condition, but in the acute period it may not have the desired effect. It has a beneficial effect on the emotional background, reduces the impact of stress factors on the body, reduces anxiety, and improves sleep.
Compatibility of Mexidol and Mildronate
The drugs in question can be used together, but subject to prescribed dosages. The simultaneous use of medications increases the therapeutic effect of each of them. However, before carrying out such a combination of drugs, it is necessary to obtain the approval of a doctor. This is due to the fact that the combination of Mexidol and Mildronate has such contraindications as:
- renal and liver failure,
- high intracranial pressure, etc.
Directions for use and dosage
Mildronate is used for long-term treatment from several weeks to several months; more precise periods are determined by the doctor. The drug is prescribed twice a day at 500 mg per dose. The maximum possible daily dosage should not exceed 2 g. Treatment of some diseases involves intravenous and parabulbar administration of the drug. Intramuscular use of the drug is not practiced due to high pain and the risk of developing allergies.
Mexidol tablets are taken orally with a large volume of water. The maximum dose of medication per day is 800 mg. The more precise dosage is determined by the doctor in each situation. The drug can be used for intravenous and intramuscular injections. In some cases, it is allowed to dilute it in an injection solution, which uses sodium chloride.
Material and methods
The study was conducted on 123 male outbred white mature mice weighing 22-25 g without somatic or infectious pathology. The animals were obtained from the Stolbovaya nursery of the State Institution NTSBMT (Moscow region). The keeping of animals complied with the standards defined by regulatory documents1.
The experimental groups were formed by random selection using body weight as the leading indicator (the spread in initial weight between and within groups did not exceed ±10%).
The study was carried out in two series: with a single and subchronic administration (5 days) of drugs, in each of which the experiment was carried out in 6 groups of 9-12 animals each. Mexidol was administered intraperitoneally in doses of 50, 100 and 200 mg/kg, the reference drug - mildronate - in doses of 50 and 100 mg/kg. Control animals received distilled water in an equivalent volume (0.1 ml per 10 g of body weight). The last injection of drugs was carried out 40 minutes before testing.
Swimming is considered a heavy physical dynamic activity. To assess the effect of the substance on physical performance, a swimming test with additional load was used, which was carried out in accordance with the methodological recommendations for the preclinical study of drugs with a nootropic type of action [8]. Each animal was placed one at a time in a vessel (18 cm in diameter and at least 40 cm high) with pre-settled water at a temperature of 25–26 °C. Swimming was performed with a weight attached to the root of the tail, the mass of which was 8% of the body weight of the mice. The animals swam with the load until they got tired. An indicator of physical fatigue was being under water for more than 10 s. At this moment the animal was quickly removed from the water. The effectiveness of the substances was assessed by the duration of swimming of the experimental groups of animals in comparison with the control groups.
Statistical processing of experimental data was carried out using statistical packages BioStat for Windows and Excel package. The average values and standard error of the mean (Mean±SEM), as well as the median and quartiles (Me, 25%÷75%) were calculated. The normality of distribution was checked using the Shapiro-Wilk test. The significance of differences was calculated using nonparametric analysis for independent variables (Mann–Whitney U test).
special instructions
Before starting treatment with the drugs in question, it is necessary to take into account how different categories of patients react to it.
Pregnancy and lactation
Mexidol and Mildronate have not been studied enough. Doctors do not have complete information about the supply of these medications along with mother's milk and their impact on the child's health. For this reason, they do not recommend taking them to women during pregnancy and breastfeeding.
Childhood
Due to insufficient study of Mildronate and Mexidol, pediatricians recommend refraining from giving these medications to children.
Elderly age
Mildronate is often prescribed to elderly patients, like Mexidol.
General information about Mexidol
The main effect of Mexidol is to reduce tissue hypoxia by improving the ability of tissues to absorb oxygen supplied by the blood. Due to this, the cognitive functions of the brain are improved, seizures of various etiologies are stopped, anxiety and stress on the body are reduced.
Thanks to its antioxidant properties, this drug slightly improves immunity. Mexidol has a strong effect on higher nervous functions. When taken, attention, thinking, and the ability to remember increase, emotional reactions are normalized, anxiety and fear are reduced, and sleep is normalized. This allows it to be widely used in neurology.
Mexidol is produced by several domestic manufacturers; it is based on a substance - ethylmethylhydroxypyridine succinate. It has various forms of release:
- pills;
- solution for injection (intramuscular, intravenous).
Side effects of Mexidol and Mildronate
The use of Mexidol often provokes the development of an allergic reaction. In some cases, the development of individual side effects of dyspepsia is observed.
When taking Mildronate, there are rarely any side effects. In some cases, patients may experience:
- allergic reactions (rashes, swelling, redness, itching),
- tachycardia,
- excitation,
- dyspeptic reactions,
- increase or decrease in atmospheric pressure.
Contraindications for use
Both medications in question are prohibited for use in the presence of an allergic reaction and individual intolerance to the drugs or components present in their composition. Mexidol is not yet recommended for use in the presence of acute liver or kidney failure.
Mildronate should not be taken if intracranial pressure is increased, especially against the background of intracranial tumors or problems with venous outflow. The drug in question should be used with caution if you have kidney or liver disease.
Contraindications and unwanted effects
Instructions for use of drugs also contain differences in the list of their contraindications and side effects.
Both drugs are not used if you are hypersensitive to their ingredients. In addition, Mildronate is contraindicated in case of intracranial hypertension, and the use of Mexidol is prohibited in case of acute liver and kidney failure.
Medicines are generally well tolerated by patients, side effects are observed in rare cases
Taking Mildronate in some cases can lead to:
- to allergic reactions (redness and rashes on the skin, swelling, etc.);
- dyspeptic symptoms in the form of belching, nausea, vomiting, heartburn;
- increase in heart rate;
- increased arousal;
- hypotension.
The use of Mexidol is fraught with:
- allergies;
- drowsiness, weakness, lethargy;
- nausea, flatulence and other dyspeptic disorders.
Negative manifestations do not appear to be life-threatening and disappear as you stop taking the medication.
Interaction with other drugs
Mexidol can be combined normally with other medications that are used in the fight against somatic diseases. This drug reduces the toxic effects of ethyl alcohol. It further enhances the effect of the following substances:
- antidepressants,
- anticonvulsants,
- benzodiazepine drugs,
- anxiolytics,
- medications to prevent Parkinson's disease.
Mildronate increases the effectiveness of cardiac glycosides when used together. The drug is compatible with drugs such as:
- anticoagulants,
- antiarrhythmic substances,
- bronchodilators,
- antianginal drugs,
- antiplatelet agents,
- diuretics.
The principle of action of the drugs
Mexidol's main effect in the human body is on the cell membrane. This drug has a membrane-protective effect, which affects lipid peroxidation of the cell wall. At the same time, the viscosity of the cell membrane decreases and its fluidity increases, the cell becomes more resistant to external influences.
The binding capacity of membrane receptors also increases, synaptic transmission and transport of neurotransmitters improves. Thanks to these effects, the nootropic effect of the drug is manifested (memory, speech, thinking improves).
The antihypoxic effect of Mexidol in cardiomyocytes manifests itself in the form of a decrease in the area of necrosis and ischemia during myocardial infarction, and an improvement in the contractility of cardiac muscle tissue. The damaging effects of hypoxia and other unfavorable factors on the human body are reduced.
Once in the body, Mildronate blocks the enzyme carnitine, while having a vasodilating effect on blood vessels, reducing platelet aggregation, and reducing the content of toxic products of anaerobic glycolysis in cells. This leads to the restoration of the relationship between the cell's need for oxygen and its supply with the blood.
Evaluation of the effectiveness and safety of Mildronate
Thus, tissues are saturated with oxygen-rich blood, and glycolysis in cells becomes more efficient. Tolerance to physical activity increases. Complex therapy for myocardial infarction, including the use of Mildronate, reduces the area of necrosis, which allows patients to recover faster and reduce the rehabilitation period.
Overdose
Both drugs must be consumed in accordance with the prescribed dosage. When taking too large a dose of Mexidol, the patient most often develops drowsiness. Mildronate is characterized by low toxicity and does not cause reactions that could affect the health of patients. Treatment of overdose should be symptomatic. Exceeding the recommended dose of Mildronate in a person can be determined by the following symptoms:
- decreased blood pressure along with headache,
- dizziness,
- tachycardia,
- general weakness of the body.
In case of overdose, it is necessary to call the patient an ambulance as quickly as possible. While she is driving, you can try to give him first aid. It should consist of gastric lavage.
Reviews
Elena, 34 years old, Kyiv My father has a strong craving for alcohol. He usually drinks for about two weeks, and it’s hard to break out of the binge. His heart begins to ache, his hands shake, convulsions appear, feelings of anxiety, fear, a depressive state gives way to aggression, and sleep is disturbed. Encodings don't help. It becomes scary for his health. The narcologist advised me to take Mexidol at the same time as Mildronate. A few days of treatment with these drugs allows dad to return to normal, he begins to feel well, and his behavior becomes adequate.
Igor, 44 years old, Moscow, university teacher Lately he has become very unbalanced. At work I lashed out at students and colleagues, my wife and children constantly irritated me, and I developed a feeling of fear. Because of his character, he was constantly in conflict with someone. Friends advised me to drink Mildronate. I started taking one capsule in the morning and evening. It was possible to fall asleep only in the morning, almost before getting up. The condition only worsened. I had to see a doctor. As it turned out, Mildronate should not be taken immediately before bedtime. The specialist advised me to undergo a course of treatment with Mexidol. The drug really helped me. Now the neurotic manifestations have disappeared. Thanks Mexidol.
Irina Vasilievna, 60 years old, pensioner Several years ago I began to feel unpleasant symptoms: strong heartbeat, alternating with interruptions, shortness of breath, chest pain on the left side. The doctor diagnosed coronary heart disease and prescribed Mildronate. The medicine is quite expensive, but completely worth it. Not only has my health improved markedly, but my performance has also increased. Now I work in the garden with my children and feel almost no fatigue.
Analogs
The most effective drugs with a similar effect as Mildronate are:
- Angiocardil,
- Vazonat,
- Energoton,
- Idrinol,
- Kardazin,
- Cardionate,
- Carduktal,
- Meldonium,
- Melfort,
- Metazidine,
- Mildrocard,
- Mildroxin,
- President,
- Riboxin,
- Triductan, etc.
The highest quality analogues of Mexidol:
- Actovegin,
- Neurox,
- Mexicofin,
- Mexico,
- Mexiprim,
- Astrox,
- Cerecard, etc.
