Possibilities of using adaptol in clinical practice

Possibilities of using adaptol in clinical practice

• Doctor of Medical Sciences, Prof. V.R. Mkrtchyan,
• Doctor of Medical Sciences, Prof., Honored Russian scientist V.A. Orlov,
• asp. L.Z. Kozhokova

Adaptol (active ingredient tetramethyltetraazabicyclooctanedione, mebicarum, OlinePharm JSC) is positioned as a drug with a wide range of clinical activity, possessing the properties of tranquilizers, nootropics, adaptogens, biocorrectors, antidepressants, lipid-lowering and antianginal agents.
Such a wide spectrum of therapeutic action is not inherent in, perhaps, any of the known drugs. Analysis of the studies conducted allows us to confidently say that adaptol has a clear tranquilizing effect. This effect of the drug is due to its normalizing effect on the balance of activity of various neurotransmitter systems of the brain: activating in relation to the inhibitory neurotransmitter GABA and weakening in relation to the excitatory neurotransmitters - norepinephrine and glutamate, as well as a normalizing effect on the relationship between adrenergic and serotonergic effects. The drug acts on the activity of structures included in the limbic-reticular complex, in particular on the emotiogenic zones of the hypothalamus. It exhibits clear central adrenolytic activity and does not have a peripheral adrenolytic effect. Like antipsychotics, it changes the permeability of the blood-brain barrier. Even in high concentrations it has no effect on isolated smooth muscle organs. Acting on the serotonergic system of the body, in small and medium doses it enhances the effect of the serotonin precursor tryptophan. It was experimentally established that the drug significantly increases the content of serotonin in the brain stem of rats.

Adaptol, being a derivative of bicyclic biureas, is a separate chemical group of tranquilizers; the drug has a pronounced anxiolytic, vegetative stabilizing, and sedative effect. Adaptol does not cause muscle relaxation, impaired coordination of movements, and does not have a hypnotic effect; it only enhances the effect of hypnotics, normalizing sleep phases. The anxiolytic effect of Adaptol consists of suppressing negative emotions, without affecting positive ones, which distinguishes it from diazepam, the use of which enhances positive emotions, which can lead to a kind of “euphoric” effect.

The drug is also used in psychiatry and to improve the tolerability of neuroleptics (reduces the inhibitory effect of chlorpromazine on the speed of reactions without enhancing the hepatotropic negative effects of chlorpromazine, has a reducing effect on neurotic and somatovegetative disorders that have arisen as side effects of neuroleptic therapy, compared with cyclodol and piracetam more intensely affecting vegetative-vascular disorders) and benzodiazepine tranquilizers (causes a decrease in muscle relaxation and an increase in the speed of psychomotor processes), antidepressants, antiepileptic drugs. At the same time, the therapeutic effectiveness of these drugs increases. Thus, adaptol does not cause pronounced behavioral toxicity and is a daytime tranquilizer that allows you to fully maintain performance when taking it.

A high degree of safety is evidenced by the intake of 30 g (100 tablets) of the drug by 2 patients with suicidal goals, which did not cause them any harm. There is a known patient who took 60 or 80 mebicarum tablets per day for 2 months as self-medication. They underwent 2 such courses, and there were no signs of intoxication in the blood, and the patient’s subjective well-being during treatment was impeccable.

The drug does not interact with other drugs and food, no metabolites are formed when it is taken, and it is excreted from the body unchanged in urine and feces. It does not accumulate in the body, and therefore there is no addiction to the drug, therefore 2-3-month courses of continuous therapy with adaptol are allowed.

The properties of adaptol make it possible to prescribe it in childhood. In child psychiatry, it is used for residual organic brain failure with a prevailing neurosis-like syndrome (sleeping, sleepwalking, night terrors), addictive behavior (hashish, heroin in combination with smoking), neuroleptic syndrome (with early dyskinesia). The drug has the most pronounced effect on affective disorders that accompany neurolepsy (anxiety, fear). To relieve neurolepsy, it is combined with benzodiszepine tranquilizers. The drug is used for neurasthenia - irritable weakness (increased excitability and easy exhaustion), anxiety-phobic disorders (anxiety, neurotic phobias, anxiety disorder due to fear of separation in childhood, generalized anxiety disorders, specific phobias, social phobias), obsessive-compulsive disorders (obsessive states). A feature of the listed disorders in children is the insufficiency or absence of personal awareness of existing disorders, the predominance of somatovegetative or movement disorders.

Unlike adults, in whom the maximum single dose of adaptol can reach 3 g, and the daily dose is 10 g, children aged 5-7 years adaptol are prescribed 0.5 g / day, at the age of 7-10 years - 0.75 g / day , at the age of 10-14 years - 1.0 g / day, at the age of 14 years and older - 1.0-1.5 g / day.

The course of continuous treatment is 1-2 months. Improvement can be observed in the 1st week of therapy. Single therapeutic doses are selected individually: from 0.1 to 0.3 g for residual organic failure; from 0.3 to 0.6 for addictive behavior, frequency of administration 2-3 times a day. The effect is observed already on the 2-3rd day of administration. The duration of treatment is 3 months for residual organic failure and 3-4 weeks for addictive behavior.

It should be noted that in pediatrics, adaptol begins to be used from 5-7 years of age. This means the possibility of its use in premenstrual syndrome, as in the literature there is data on the effectiveness of adaptol therapy from the 14th-18th day of the menstrual cycle until the onset of menstrual bleeding, 2-3 courses of treatment. The drug eliminates vegetative-vascular dystonia and emotional manifestations of the disease. However, no studies have been conducted in girls aged 11–14 years.

It can be assumed that the drug has a positive effect in adolescents with psychovegetative disorders of various origins.

In addition, adaptol is recommended for parents when initially contacting a psychiatrist in a state of anxiety, anxious anticipation of a “terrible” diagnosis in a child.

The use of the drug in obstetric practice revealed its affinity for placental membranes; the drug accumulates in the placenta and causes a pronounced dilating effect on the uterine and placental vessels. The use of mebicarum led to the normalization of disorders in all parts of the functional system mother-placenta-fetus. The drug increases the specific activity of the kallikrein-kinin system, which enhances the vasodilator effect. The use of mebicarum normalized the condition of the fetus during hypoxia due to the normalization of uteroplacental blood flow and a direct effect on the functions of fetal centers that regulate homeostasis and activation of the hormonal function of the placenta. The drug was used starting from the 28th week of pregnancy at the rate of 20-25 mg per 1 kg of body weight of the pregnant woman in 4-5 doses per day for 6-7 days. The vasodilating effect of mebicarum occurred on days 2-3 and persisted for a long time.

The nootropic effect of adaptol can also be considered proven. Even in studies on mebicarum, comparison of the nootropic effect of the drug with piracetam and pyriditol made it possible to identify a harmonious spectrum of nootropic action of mebicarum. In elderly patients with organic brain lesions and schizophrenia with a disease duration of more than 10 years, mebicarum monotherapy for 3-4 weeks in doses of 0.3-1.5 g/day was more effective than compared drugs in patients with symptoms of hyperesthesia, emotional and vegetative lability, increased emotional excitability and intense emotional experiences. Clinical manifestations of weakened memory and understanding were subject to greater reduction. At the same time, pyriditol was superior to compared drugs in its effect on abulia, motor retardation, decreased affect, and increased exhaustion, and piracetam was most effective in ideational retardation and was comparable to pyriditol in its effect on apathy. Vasovegetative disorders decreased with treatment with all drugs to the same extent. The authors associate the harmonious nature of the nootropic spectrum of action of mebicarum with its optimizing effect on the thinking of patients. At the same time, the stimulating component in the action of pyriditol and piracetam introduces fussiness and irritability into the behavior of patients, and reduces the active inhibition necessary for targeted volitional and intellectual efforts. In addition, mebicarum had a normalizing effect on deficit thinking disorders in patients with paranoid schizophrenia, reduced symptoms such as paralogy, reasoning, incoherence, and did not stimulate any disorders in this area. Mebicarum contributed to a change in the type of thinking from the “right hemisphere” - emotional, concrete and figurative, to the “left hemisphere” - predominantly verbal, abstract and logical, and piracetam enhanced the “right hemisphere” features of thinking - emotionality, imagery and concreteness. The dose dependence of the nootropic effect of mebicarum has been established. When prescribing small doses of the drug (0.9 g/day), the psychostimulating and antidepressant effect is more pronounced, at medium doses (1.8-2.7 g/day) - antiasthenic and nootropic, at high doses (4.5 g/day) ) - sedative.

According to data obtained by S.A. Zhivolupov et al., adaptol improves neuroplasticity processes by increasing the level of one of the neurotrophic growth factors, brain-derived neurotrophic factor (BDNF), in patients with certain functional and organic diseases of the nervous system. The use of the drug in complex therapy of patients with somatoform dysfunction of the autonomic nervous system and the consequences of closed craniocerebral injury, in addition to regression of clinical symptoms, 30 days after the start of treatment led to a significant increase in the level of BDNF in the blood, and this effect was dose-dependent and more pronounced at a daily dose of adaptol 3000 mg than at a dose of 1500 mg.

Many studies have noted the ability of the drug to normalize the functioning parameters of various, sometimes multidirectional, changes in many body systems. When treated with adaptol, the tolerability of conditions that require tension in adaptation processes improves, which is considered as the adaptogenic activity of this drug. Thus, in patients with long-term consequences of exposure to ionizing radiation, 16 years after the accident at the Chernobyl nuclear power plant, who received against the background of traditional therapy (nootropics, cardiotrophics, vascular drugs, vitamins) mebicarum for 2 weeks on the 1st day - 300 mg, during 2-3 days - 600 mg, then 900 mg (300 mg 3 times a day) until the end of the course, the effectiveness of therapy increased on average 2 times for leading symptoms (irritability, anxiety, sleep disturbances, blood pressure normalized and heart activity, decreased severity of headaches and shortness of breath during emotional experiences) and decreased addiction to smoking. Moreover, positive results were achieved already in the 1st week of treatment.

In case of tobacco addiction, data have been obtained on a decrease in the desire to smoke and alleviation of withdrawal disorders with the use of mebicarum in complex therapy at a dose of 0.6 g 3 times a day for 3-4 weeks.

Mebicarum in doses of 1.5-2.1 g/day for 3-4 weeks eliminates or weakens the severity of borderline mental disorders in patients with alcoholism - asthenia, irritability, emotional lability, dysphoria, craving for alcohol. In addition, mebicarum increases the synthesis of endogenous alcohol in the body of patients by approximately 75% - 2 times more than after taking sodium hydroxybutyrate, and 4 times more than after taking seduxen. It is the increase in the concentration of alcohol in the blood of patients to normal that leads to a decrease and disappearance of the need for alcohol after taking 1.5 g of mebicarum.

In the treatment of chronic alcoholism with the calculation of an individual dosage regimen, based on an assessment of the drug content in the blood plasma during the development of the tranquilizing effect, after taking a single dose, effective elimination of psychopathological disorders was ensured.

According to the data available in the literature, the use of the drug is considered effective for non-coronary cardialgia of various origins, with the exception of cardialgia associated with spinal osteochondrosis. In climacteric syndrome, mebicarum affects the manifestations of cardiac syndrome: eliminates or weakens pain, shortness of breath, palpitations; normalizes repolarization processes in the myocardium and central hemodynamic parameters. Also eliminates or weakens other manifestations of menopausal syndrome: hot flashes, paresthesia, headaches, fatigue; normalizes sleep. It is known that currently, menopausal syndrome is considered largely as a process of adaptation of the body to new conditions of hormonal regulation.

If the listed properties of adaptol can largely be explained by its central mechanism of action, then the remaining described effects of the drug clearly require explanation.

So, according to L.O. Gromova et al., in the mechanisms of action of adaptol there is a direct antioxidant effect, which consists in the ability to inhibit the peroxidation of not only lipids, but also proteins.

When using the drug as a tranquilizer, its hypolipidemic effect was noted.

Mebicarum at a dose of 1.8 g/day for 3 weeks reduced the content of total cholesterol (TC) in the blood plasma by 36%, very low density lipoprotein cholesterol (VLDL) by 28%, low density lipoprotein cholesterol (LDL) by 20.4%, triglycerides (TG) - by 23% and increased the level of high-density lipoproteins (HDL) - by 47% compared to the initial level. At a dose of 1.2 g/day, after 2 weeks of treatment, mebicarum reduced the level of total cholesterol in the blood plasma by 28%, LDL cholesterol by 21% and increased the level of HDL cholesterol by 32%. According to the same authors, the drug corrects the proatherogenic effect of β-blockers. To clarify whether the hypocholesterolemic effect of mebicarum is a consequence of its psychotropic activity or this is its original specific property, a comparative experimental study was conducted on the effect of mebicarum (250 mg/kg) and diazepam (2 mg/kg) on ​​lipid metabolism in rats. Mebicarum, unlike diazepam, reduced the level of LDL cholesterol by 27.4% and increased the level of HDL cholesterol by 48%. This indicates that the antihyperlipidemic effect of mebicarum is not related to its psychotropic activity, but is a specific feature.

In an experiment on rats, hypokinesia for 14 days led to a decrease in animal body weight, an increase in the relative weight of the adrenal glands, an increase in the content of total cholesterol, TG, malondialdehyde and a decrease in the level of HDL cholesterol and phospholipids. The use of mebicarum not only prevented a decrease in the body weight of rats and an increase in the mass of the adrenal glands, but also led to a decrease in total cholesterol, TG and the level of malondialdehyde, as well as an increase in the content of HDL cholesterol and phospholipids, which made it possible to state that mebicarum has a combination of adaptogenic, hypolipidemic and antioxidant properties .

A similar antihyperlipidemic effect of the drug was found when reproducing nutritional hypercholesterolemia in rabbits. Thus, mebicarum also has an antihyperlipidemic effect in models of hypercholesterolemia not associated with stress effects on lipid metabolism.

Unlike benzodiazepine tranquilizers, mebicarum enhances the contractile function of the myocardium, increases systolic and cardiac output, and accelerates blood flow in the aorta. The cardiac stimulating effect of the drug is also manifested in an isolated heart and in conditions of blockade of beta-adrenergic receptors of the heart. Mebicarum increases the volumetric velocity of coronary blood flow, the strength and duration of this effect depends on the dose of the drug and ranges from 15 to 35 minutes. In parallel with the increase in coronary blood flow, the absorption of oxygen by the heart increases, but to a much lesser extent, therefore the content of oxyhemoglobin in the venous blood increases. Experiments on various models of acute coronary insufficiency (ligation of the descending branch of the left coronary artery, dosed narrowing of the coronary artery with simultaneous imposition of a high contraction rhythm on the heart) revealed a positive effect of mebicarum on ischemic myocardium: ST segment elevation decreased, the ratio of lactate and pyruvate in the blood flowing from the heart was normalized. ischemic zones.

At doses of 200-500 mg/kg, mebicarum expanded the peripheral (femoral) arteries, reducing their resistance to blood flow, which was not due to a direct myotropic effect, but was realized through neurogenic sympathetic tone. At the same doses, mebicarum suppressed the bioelectrical activity of the sympathetic nerves of the kidneys and heart.

According to clinical studies, a good and satisfactory antianginal effect was observed in approximately 70% of patients with angina pectoris. Their mood improved, the number of anginal attacks and daily consumption of nitroglycerin decreased by 2-4 times. In patients with angina pectoris of functional class II, tolerance to dosed physical activity increased. The authors believe that for angina of functional class I and II, mebicarum can be considered as an independent antianginal agent; for more severe angina, it is recommended to be used in combination with nitrates and β-adrenergic blockers.

Mebicarum had an analgesic effect in the acute period of myocardial infarction (MI), enhanced the analgesic effect of fentanyl and eliminated its side effects on the cardiovascular system.

The use of mebicarum during the rehabilitation period in patients who had suffered an MI helped to improve their coronary blood flow, expand the range of physical activities, and reduce fear of them. According to I.E. Zimakova et al., improvement of oxygen balance in the heart muscle occurred due to an increase in coronary blood flow, antihypoxic effect, decrease in blood viscosity and intravascular aggregation of erythrocytes.

Patients with post-infarction cardiosclerosis and the presence of psychosomatic pathology (high level of personal anxiety, anxious-asthenic, anxious-phobic states) in addition to standard therapy with nitrates, angiotensin-converting enzyme inhibitors, β-blockers, aldosterone antagonists, disaggregants, statins, trimetazidine in one group were prescribed the anxiolytic adaptol at a dose of 500 mg 2 times a day, on the other - standard therapy and placebo adaptol. Observation continued for 1 month. An assessment of the quality of life showed that the addition of adaptol contributed to an increase in mental resistance to stressful situations and an improvement in the psychological adaptation of patients who had suffered an MI. Indicators of social functioning remained virtually unchanged in both groups. The antianginal effect of adaptol was observed due to a decrease in the frequency of angina attacks that occurred after psycho-emotional stress, with angina pectoris of physical exertion; there were no differences between the groups.

Among the patients included in the study, an analysis of the quality of life in chronic heart failure stages I-IIA was carried out in both groups. In the adaptol group, the quality of life increased in a significantly larger number of patients due to the physical and emotional spheres, in the group receiving standard therapy and placebo, mainly due to improved physical indicators.

In a later study of the therapeutic potential of adaptol in the early post-infarction period (3-4 weeks after MI) in patients with anxiety disorders, the authors concluded that adaptol at a dose of 1500-2000 mg/day after 28-30 days of therapy has an anxiolytic, stress-protective, vegetative-normalizing and anti-asthenic effects, eliminates sleep disturbances by accelerating the process of falling asleep, reducing the number of night and early morning awakenings; reduces the sympathetic effect on the activity of the heart, helping to normalize autonomic reactivity. The authors indicate that the administration of adaptol as part of basic therapy improves the clinical course of the post-infarction period, reduces the number of anginal attacks, while reducing the frequency of taking nitroglycerin tablets, and increases the distance covered during the 6-minute walk test. At the same time, no adverse interaction of adaptol with drugs in the basic therapy of chronic heart failure: nitrates, β-blockers, angiotensin-converting enzyme inhibitors, diuretics was detected.

According to available data, in addition to the work of R.A. Camburg et al. (1986), which indicates the possibility of considering adaptol as an independent antianginal agent, all subsequent work proves an increase in the antianginal effect in patients with angina pectoris and in the post-infarction period only if angina pectoris was caused by stress or the presence of anxiety disorders. Thus, the question of whether adaptol has an independent antianginal effect remains open.

The inclusion of adaptol in addition to antihypertensive therapy in patients with post-infarction cardiosclerosis with hypertension was accompanied by more pronounced positive dynamics in the variability of systolic and diastolic blood pressure during the day and night than in the placebo group.

The inclusion of adaptol in the treatment regimen increased the severity of the lipid-lowering effect of the combination of statins and adaptol compared to statins. According to L.A. Lapshina, P.G. Kravchun, O.S. Shevchenko (2008), correction of psychopathological manifestations and oxidative stress by adaptol in patients who have suffered a myocardial infarction is evidence of the specific effect of adaptol in correcting the lipid composition of the blood and seems especially important in patients who have suffered an acute MI.

Compared with standard therapy for patients with post-infarction cardiosclerosis, the addition of adaptol to it led to a more pronounced positive effect on the processes of free radical oxidation (decrease in pro-oxidant and increase in antioxidant activity). V.N. Kovalenko et al. (2006) showed that the addition of adaptol to the complex therapy of hypertension and neurocirculatory dystonia contributed to the improvement of heart rate variability parameters with a decrease in the activity of the sympathetic division of the autonomic nervous system, restoring its balance with normalization of the regulation of heart activity.

In the work of L.M. Vasilets et al. The structure of heart rhythm disturbances and the features of temporal analysis of heart rate variability in patients with the syndrome and phenomenon of premature excitation of the ventricles were studied. It was shown that the use of adaptol in a dose of 500 mg 2 times a day for 60 days against the background of antiarrhythmic therapy with amiodarone helped to reduce autonomic imbalance and reduced the arrhythmogenic readiness of the myocardium.

The antihyperlipidemic, antioxidant, and anti-ischemic effects of the drug obtained experimentally and clinically cannot in any way be due only to the studied central mechanisms of its action. And if the antioxidant effect of the drug can also be explained by the fact that the drug molecule contains two methylated urea fragments, and urea is considered as a reference antioxidant, then the antihyperlipidemic and antianginal effects of the drug cannot be associated only with its central and antioxidant action. In this regard, it is of particular interest to directly study the mechanisms of the drug’s influence on lipid metabolism, the peroxidation system, and especially coronary blood flow, both experimentally and in clinical practice, especially taking into account the effect of the drug on the chemical activity of water.

There is evidence that extremely high-frequency (EHF; millimeter waves) irradiation stimulates cellular receptors of a protein nature due to the activation of the aqueous component of the extracellular fluid. At the same time, the fraction of mobile, chemically active H2O molecules increases. The introduction into the biological environment of certain low-molecular substances that destabilize the structure of water can simulate the effects of EHF irradiation. This effect is inherent in urea. Under its influence, the generation of a fraction of mobile water molecules in solution and, along with this, the depletion of a fraction of bulk water not included in the fraction of mobile molecules was revealed. Depletion of the bulk water fraction was correlated with the instability of proteins such as chymotrypsinogen and serum albumin (denaturation). The authors believe that since the unfolding of the protein globule is preceded by an increase in intraglobular mobility, the denaturation effect manifests both direct and indirect effects of urea on protein dynamics through the destruction of the water structure.

The structural determinant of the urea fragment, which is responsible for its ability to generate mobile water molecules, has been established: the presence of two close and parallel N–H bonds.

Similar properties were found in mebicarum. Urea and mebicarum activate water as a nucleophilic reagent. An increase in the chemical activity of water is associated with the destruction of the structure of water, i.e. with an increase in the proportion of rotator molecules. Most likely, all this determines the unusually wide range of pharmaceutical activity of the anxiolytic mebicarum without its inclusion in metabolism and in the absence of specific receptors.

The above can largely shed light on the unique, multifaceted spectrum of clinical effectiveness of adaptol and proves the need for a deeper study and detailed mechanisms of action of the drug in such various pathological processes both in the clinic and in experiments.

3.4

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Adaptol

Adaptol (tetramethyltetraazabicyclooctanedione) is an anxiolytic (anti-anxiety) drug. It has a wide range of medical indications and can be used for the treatment and prevention of a number of common psychosomatic pathologies. Well tolerated by patients. Allowed for use in pediatric as well as geriatric practice. Is the so-called "a daytime tranquilizer." It has moderate sedative activity, eliminates or softens manifestations of anxiety, anxiety, psycho-emotional stress, and increased aggressiveness. It does not have a muscle relaxant effect, does not impair coordination, does not depress cognitive activity, and does not affect physical performance, which allows the drug to be used for any type of activity. Without having its own hypnotic effect, the drug potentiates the effect of co-administered sleeping pills, improving sleep quality and reducing the number of unmotivated night awakenings. Adaptol has a very high toxicity threshold, because... in its chemical structure it is very close to substances formed in the human body as a result of natural metabolic transformations. Does not cause pathological addiction. Removes the body from the influence of the sympathetic nervous system, which allows the drug to be used in the treatment of vegetative-vascular dystonia, relief of symptoms of premenstrual syndrome, and chronic fatigue. Does not cause euphoria or high spirits. Adaptol neutralizes the aggressive effect of free radicals and allows you to better tolerate oxygen starvation, which makes it possible to use it in cases of circulatory disorders in internal organs and in cases of hypoxic damage.

The “ginseng-like” effect of Adaptol is in demand in situations where it is necessary to support the nervous system in case of disruption of internal regulation and increased stress. The drug has a wide therapeutic range: it is used for neuroses accompanied by psycho-emotional instability and irritability, for cardialgia of non-ischemic origin, to improve the tolerability of drugs of other pharmacological groups (benzodiazepine tranquilizers, antipsychotics). Tetramethyltetraazabicyclooctanedione is chemically inert, which allows it to be combined with other drugs. In addition to the mentioned tranquilizers and neuroleptics, these are antidepressants, sleeping pills, psychostimulants, nootropics. Another advantage of Adaptol is its effectiveness in eliminating or suppressing symptoms of nicotine withdrawal. The drug also has a moderate nootropic effect, stimulates cognitive activity (memory, attention, concentration, intellectual activity), without exacerbating the symptoms of psychopathological disorders. A decrease in blood pressure or body temperature is not a reason to discontinue Adaptol: in the future, these indicators will return to normal on their own. Allergic reactions, in turn, require stopping the medication course and prescribing another drug. Cases of overdose with Adaptol have not been described in the specialized medical literature. The drug can be used in combination with antidepressants, antipsychotics, sedatives and hypnotics.

Adaptol (active ingredient tetramethyltetraazabicyclooctanedione, mebicarum, OlinePharm JSC) is positioned as a drug with a wide range of clinical activity, possessing the properties of tranquilizers, nootropics, adaptogens, biocorrectors, antidepressants, lipid-lowering and antianginal agents [7]. Such a wide spectrum of therapeutic action is not inherent in, perhaps, any of the known drugs.

Analysis of the studies conducted allows us to confidently say that adaptol has a clear tranquilizing effect. This effect of the drug is due to its normalizing effect on the balance of activity of various neurotransmitter systems of the brain: activating in relation to the inhibitory neurotransmitter GABA and weakening in relation to the excitatory neurotransmitters - norepinephrine and glutamate, as well as a normalizing effect on the relationship between adrenergic and serotonergic effects. The drug acts on the activity of structures included in the limbic-reticular complex, in particular on the emotiogenic zones of the hypothalamus. It exhibits clear central adrenolytic activity and does not have a peripheral adrenolytic effect. Like antipsychotics, it changes the permeability of the blood-brain barrier. Even in high concentrations it has no effect on isolated smooth muscle organs. Acting on the serotonergic system of the body, in small and medium doses it enhances the effect of the serotonin precursor tryptophan. It was experimentally established that the drug significantly increases the content of serotonin in the brain stem of rats.

Adaptol, being a derivative of bicyclic biureas, is a separate chemical group of tranquilizers; the drug has a pronounced anxiolytic, vegetative stabilizing, and sedative effect. Adaptol does not cause muscle relaxation, impaired coordination of movements, and does not have a hypnotic effect; it only enhances the effect of hypnotics, normalizing sleep phases. The anxiolytic effect of Adaptol consists of suppressing negative emotions, without affecting positive ones, which distinguishes it from diazepam, the use of which enhances positive emotions, which can lead to a kind of “euphoric” effect.

The drug is also used in psychiatry and to improve the tolerability of neuroleptics (reduces the inhibitory effect of chlorpromazine on the speed of reactions without enhancing the hepatotropic negative effects of chlorpromazine, has a reducing effect on neurotic and somatovegetative disorders that have arisen as side effects of neuroleptic therapy, compared with cyclodol and piracetam more intensely affecting vegetative-vascular disorders) and benzodiazepine tranquilizers (causes a decrease in muscle relaxation and an increase in the speed of psychomotor processes), antidepressants, antiepileptic drugs. At the same time, the therapeutic effectiveness of these drugs increases. Thus, adaptol does not cause pronounced behavioral toxicity and is a daytime tranquilizer that allows you to fully maintain performance when taking it [1].

A high degree of safety is evidenced by the intake of 30 g (100 tablets) of the drug by 2 patients with suicidal goals, which did not cause them any harm. There is a known patient who took 60 or 80 mebicarum tablets per day for 2 months as self-medication. They underwent 2 such courses, and there were no signs of intoxication in the blood, and the patient’s subjective well-being during treatment was impeccable [7].

The drug does not interact with other drugs and food, no metabolites are formed when it is taken, and it is excreted unchanged from the body in urine and feces. It does not accumulate in the body, and therefore there is no addiction to the drug, therefore 2-3-month courses of continuous therapy with adaptol are allowed.

The described properties of adaptol make it possible to prescribe it in childhood [16, 20]. In child psychiatry, it is used for residual organic brain failure with a prevailing neurosis-like syndrome (sleeping, sleepwalking, night terrors), addictive behavior (hashish, heroin in combination with smoking), neuroleptic syndrome (with early dyskinesia). The drug has the most pronounced effect on affective disorders that accompany neurolepsy (anxiety, fear). To relieve neurolepsy, it is combined with benzodiszepine tranquilizers. The drug is used for neurasthenia - irritable weakness (increased excitability and easy exhaustion), anxiety-phobic disorders (anxiety, neurotic phobias, anxiety disorder due to fear of separation in childhood, generalized anxiety disorders, specific phobias, social phobias), obsessive-compulsive disorders (obsessive states). A feature of the listed disorders in children is the insufficiency or absence of personal awareness of existing disorders, the predominance of somatovegetative or movement disorders.

Unlike adults, in whom the maximum single dose of adaptol can reach 3 g, and the daily dose is 10 g, children aged 5-7 years adaptol are prescribed 0.5 g / day, at the age of 7-10 years - 0.75 g / day , at the age of 10-14 years - 1.0 g / day, at the age of 14 years and older - 1.0-1.5 g / day.

The course of continuous treatment is 1-2 months. Improvement can be observed in the 1st week of therapy.

Single therapeutic doses are selected individually: from 0.1 to 0.3 g for residual organic failure; from 0.3 to 0.6 for addictive behavior, frequency of administration 2-3 times a day. The effect is observed already on the 2-3rd day of administration. The duration of treatment is 3 months for residual organic failure and 3-4 weeks for addictive behavior.

It should be noted that in pediatrics, adaptol begins to be used from 5-7 years of age. This means the possibility of its use in premenstrual syndrome, as in the literature there is data on the effectiveness of adaptol therapy from the 14th-18th day of the menstrual cycle until the onset of menstrual bleeding, 2-3 courses of treatment. The drug eliminates vegetative-vascular dystonia and emotional manifestations of the disease. However, no studies have been conducted in girls aged 11–14 years.

It can be assumed that the drug has a positive effect in adolescents with psychovegetative disorders of various origins.

In addition, adaptol is recommended for parents when initially contacting a psychiatrist in a state of anxiety, anxious anticipation of a “terrible” diagnosis in a child.

The use of the drug in obstetric practice revealed its affinity for placental membranes; the drug accumulates in the placenta and causes a pronounced dilating effect on the uterine and placental vessels [15]. The use of mebicarum led to the normalization of disorders in all parts of the functional system mother-placenta-fetus. The drug increases the specific activity of the kallikrein-kinin system, which enhances the vasodilator effect. The use of mebicarum normalized the condition of the fetus during hypoxia due to the normalization of uteroplacental blood flow and a direct effect on the functions of fetal centers that regulate homeostasis and activation of the hormonal function of the placenta. The drug was used starting from the 28th week of pregnancy at the rate of 20-25 mg per 1 kg of body weight of the pregnant woman in 4-5 doses per day for 6-7 days. The vasodilating effect of mebicarum occurred on days 2-3 and persisted for a long time.

The nootropic effect of adaptol can also be considered proven. Even in studies on mebicarum, a comparison of the nootropic effect of the drug with piracetam and pyriditol [11] made it possible to identify a harmonious spectrum of nootropic action of mebicarum. In elderly patients with organic brain lesions and schizophrenia with a disease duration of more than 10 years, mebicarum monotherapy for 3-4 weeks in doses of 0.3-1.5 g/day was more effective than compared drugs in patients with symptoms of hyperesthesia, emotional and vegetative lability, increased emotional excitability and intense emotional experiences [10]. Clinical manifestations of weakened memory and understanding were subject to greater reduction. At the same time, pyriditol was superior to compared drugs in its effect on abulia, motor retardation, decreased affect, and increased exhaustion, and piracetam was most effective in ideational retardation and was comparable to pyriditol in its effect on apathy. Vasovegetative disorders decreased with treatment with all drugs to the same extent. The authors associate the harmonious nature of the nootropic spectrum of action of mebicarum with its optimizing effect on the thinking of patients. At the same time, the stimulating component in the action of pyriditol and piracetam introduces fussiness and irritability into the behavior of patients, and reduces the active inhibition necessary for targeted volitional and intellectual efforts. In addition, mebicarum had a normalizing effect on deficit thinking disorders in patients with paranoid schizophrenia, reduced symptoms such as paralogy, reasoning, incoherence, and did not stimulate any disorders in this area. Mebicarum contributed to a change in the type of thinking from the “right hemisphere” - emotional, concrete and figurative, to the “left hemisphere” - predominantly verbal, abstract and logical, and piracetam enhanced the “right hemisphere” features of thinking - emotionality, imagery and concreteness. The dose dependence of the nootropic effect of mebicarum has been established. When prescribing small doses of the drug (0.9 g/day), the psychostimulating and antidepressant effect is more pronounced, at medium doses (1.8-2.7 g/day) - antiasthenic and nootropic, at high doses (4.5 g/day) ) - sedative.

According to data obtained by S.A. Zhivolupov et al. [5], adaptol improves neuroplasticity processes by increasing the level of one of the neurotrophic growth factors, brain-derived neurotrophic factor (BDNF), in patients with certain functional and organic diseases of the nervous system. The use of the drug in complex therapy of patients with somatoform dysfunction of the autonomic nervous system and the consequences of closed craniocerebral injury, in addition to regression of clinical symptoms, 30 days after the start of treatment led to a significant increase in the level of BDNF in the blood, and this effect was dose-dependent and more pronounced at a daily dose of adaptol 3000 mg than at a dose of 1500 mg.

Many studies have noted the ability of the drug to normalize the functioning parameters of various, sometimes multidirectional, changes in many body systems. When treated with adaptol, the tolerability of conditions that require tension in adaptation processes improves, which is considered as the adaptogenic activity of this drug. Thus, in patients with long-term consequences of exposure to ionizing radiation, 16 years after the accident at the Chernobyl nuclear power plant, who received against the background of traditional therapy (nootropics, cardiotrophics, vascular drugs, vitamins) mebicarum for 2 weeks on the 1st day - 300 mg, during 2-3 days - 600 mg, then 900 mg (300 mg 3 times a day) until the end of the course, the effectiveness of therapy increased on average 2 times for leading symptoms (irritability, anxiety, sleep disturbances, blood pressure normalized and heart activity, decreased severity of headaches and shortness of breath during emotional experiences) and decreased addiction to smoking. Moreover, positive results were achieved already in the 1st week of treatment [9].

In case of tobacco addiction, data have been obtained on a decrease in the craving for smoking and relief of withdrawal disorders when using mebicarum in complex therapy at a dose of 0.6 g 3 times a day for 3-4 weeks.

Mebicarum in doses of 1.5-2.1 g/day for 3-4 weeks eliminates or weakens the severity of borderline mental disorders in patients with alcoholism - asthenia, irritability, emotional lability, dysphoria, craving for alcohol. In addition, mebicarum increases the synthesis of endogenous alcohol in the body of patients by approximately 75% - 2 times more than after taking sodium hydroxybutyrate, and 4 times more than after taking seduxen. It is the increase in the concentration of alcohol in the blood of patients to normal that leads to a decrease and disappearance of the need for alcohol after taking 1.5 g of mebicarum.

In the treatment of chronic alcoholism with the calculation of an individual dosage regimen based on the assessment of the drug content in the blood plasma during the development of the tranquilizing effect, after taking a single dose, effective elimination of psychopathological disorders was ensured [19].

According to the data available in the literature, the use of the drug is considered effective for non-coronary cardialgia of various origins, with the exception of cardialgia associated with spinal osteochondrosis. In climacteric syndrome, mebicarum affects the manifestations of cardiac syndrome: eliminates or weakens pain, shortness of breath, palpitations; normalizes repolarization processes in the myocardium and central hemodynamic parameters. Also eliminates or weakens other manifestations of menopausal syndrome: hot flashes, paresthesia, headaches, fatigue; normalizes sleep [14]. It is known that currently, menopausal syndrome is considered largely as a process of adaptation of the body to new conditions of hormonal regulation.

If the listed properties of adaptol can largely be explained by its central mechanism of action, then the remaining described effects of the drug clearly require explanation [13].

So, according to L.O. Gromova et al. [4], in the mechanisms of action of adaptol there is a direct antioxidant effect, which consists in the ability to inhibit the peroxidation of not only lipids, but also proteins.

When using the drug as a tranquilizer, its hypolipidemic effect was noted. Mebicarum at a dose of 1.8 g/day for 3 weeks reduced the content of total cholesterol (TC) in the blood plasma by 36%, very low density lipoprotein cholesterol (VLDL) by 28%, low density lipoprotein cholesterol (LDL) by 20.4%, triglycerides (TG) - by 23% and increased the level of high-density lipoproteins (HDL) - by 47% compared to the initial level.

At a dose of 1.2 g/day, after 2 weeks of treatment, mebicarum reduced the level of total cholesterol in the blood plasma by 28%, LDL cholesterol by 21%, and increased the level of HDL cholesterol by 32% [6]. According to the same authors, the drug corrects the proatherogenic effect of β-blockers. To clarify whether the hypocholesterolemic effect of mebicarum is a consequence of its psychotropic activity or this is its original specific property, a comparative experimental study was conducted on the effect of mebicarum (250 mg/kg) and diazepam (2 mg/kg) on ​​lipid metabolism in rats [17]. Mebicarum, unlike diazepam, reduced the level of LDL cholesterol by 27.4% and increased the level of HDL cholesterol by 48%. This indicates that the antihyperlipidemic effect of mebicarum is not related to its psychotropic activity, but is a specific feature.

In the experiment

in rats [8], hypokinesia for 14 days led to a decrease in animal body weight, an increase in the relative weight of the adrenal glands, an increase in the content of total cholesterol, TG, malondialdehyde and a decrease in the level of HDL cholesterol and phospholipids. The use of mebicarum not only prevented a decrease in the body weight of rats and an increase in the mass of the adrenal glands, but also led to a decrease in total cholesterol, TG and the level of malondialdehyde, as well as an increase in the content of HDL cholesterol and phospholipids, which made it possible to state that mebicarum has a combination of adaptogenic, hypolipidemic and antioxidant properties .

A similar antihyperlipidemic effect of the drug was found when reproducing nutritional hypercholesterolemia in rabbits. Thus, mebicarum also has an antihyperlipidemic effect in models of hypercholesterolemia not associated with stress effects on lipid metabolism [17].

Unlike benzodiazepine tranquilizers, mebicarum enhances the contractile function of the myocardium, increases systolic and cardiac output, and accelerates blood flow in the aorta. The cardiac stimulating effect of the drug is also manifested in an isolated heart and in conditions of blockade of beta-adrenergic receptors of the heart. Mebicarum increases the volumetric velocity of coronary blood flow, the strength and duration of this effect depends on the dose of the drug and ranges from 15 to 35 minutes. In parallel with the increase in coronary blood flow, the absorption of oxygen by the heart increases, but to a much lesser extent, therefore the content of oxyhemoglobin in the venous blood increases. Experiments on various models of acute coronary insufficiency (ligation of the descending branch of the left coronary artery, dosed narrowing of the coronary artery with simultaneous imposition of a high contraction rhythm on the heart) revealed a positive effect of mebicarum on ischemic myocardium: ST segment elevation decreased, the ratio of lactate and pyruvate in the blood flowing from the heart was normalized. ischemic zones.

At doses of 200-500 mg/kg, mebicarum expanded the peripheral (femoral) arteries, reducing their resistance to blood flow, which was not due to a direct myotropic effect, but was realized through neurogenic sympathetic tone. At the same doses, mebicarum suppressed the bioelectrical activity of the sympathetic nerves of the kidneys and heart.

According to clinical studies

[7], a good and satisfactory antianginal effect was observed in approximately 70% of patients with angina pectoris. Their mood improved, the number of anginal attacks and daily consumption of nitroglycerin decreased by 2-4 times. In patients with angina pectoris of functional class II, tolerance to dosed physical activity increased. The authors believe that for angina of functional class I and II, mebicarum can be considered as an independent antianginal agent; for more severe angina, it is recommended to be used in combination with nitrates and β-blockers.

Mebicarum had an analgesic effect in the acute period of myocardial infarction (MI), enhanced the analgesic effect of fentanyl and eliminated its side effects on the cardiovascular system [4].

The use of mebicarum during the rehabilitation period in patients who had suffered an MI helped to improve their coronary blood flow, expand the range of physical activities, and reduce fear of them. According to I.E. Zimakova et al. [7], an improvement in the oxygen balance in the heart muscle occurred due to an increase in coronary blood flow, an antihypoxic effect, a decrease in blood viscosity and intravascular aggregation of erythrocytes.

Patients with post-infarction cardiosclerosis and the presence of psychosomatic pathology (high level of personal anxiety, anxious-asthenic, anxious-phobic states) in addition to standard therapy with nitrates, angiotensin-converting enzyme inhibitors, β-blockers, aldosterone antagonists, disaggregants, statins, trimetazidine in one group were prescribed the anxiolytic adaptol at a dose of 500 mg 2 times a day, on the other - standard therapy and placebo adaptol. Observation continued for 1 month. An assessment of the quality of life showed that the addition of adaptol contributed to an increase in mental resistance to stressful situations and an improvement in the psychological adaptation of patients who had suffered an MI. Indicators of social functioning remained virtually unchanged in both groups. The antianginal effect of adaptol was observed due to a decrease in the frequency of angina attacks that occurred after psycho-emotional stress, with angina pectoris of physical exertion; there were no differences between the groups.

Among the patients included in the study, an analysis of the quality of life in chronic heart failure stages I-IIA was carried out in both groups. In the adaptol group, the quality of life increased in a significantly larger number of patients due to the physical and emotional spheres, in the group receiving standard therapy and placebo, mainly due to improved physical indicators.

In a later study of the therapeutic potential of adaptol in the early post-infarction period (3-4 weeks after MI) in patients with anxiety disorders, the authors [18] concluded that adaptol at a dose of 1500-2000 mg/day after 28-30 days of therapy has anxiolytic, stress-protective, vegetative-normalizing and anti-asthenic effects, eliminates sleep disorders by accelerating the process of falling asleep, reducing the number of night and early morning awakenings; reduces the sympathetic effect on the activity of the heart, helping to normalize autonomic reactivity. The authors indicate that the administration of adaptol as part of basic therapy improves the clinical course of the post-infarction period, reduces the number of anginal attacks, while reducing the frequency of taking nitroglycerin tablets, and increases the distance covered during the 6-minute walking test. At the same time, no adverse interaction of adaptol with drugs in the basic therapy of chronic heart failure: nitrates, β-blockers, angiotensin-converting enzyme inhibitors, diuretics was detected.

According to available data, in addition to the work of R.A. Camburg et al. (1986), which indicates the possibility of considering adaptol as an independent antianginal agent, all subsequent work proves an increase in the antianginal effect in patients with angina pectoris and in the post-infarction period only if angina pectoris was caused by stress or the presence of anxiety disorders. Thus, the question of whether adaptol has an independent antianginal effect remains open.

The inclusion of adaptol in addition to antihypertensive therapy in patients with post-infarction cardiosclerosis with hypertension was accompanied by more pronounced positive dynamics in the variability of systolic and diastolic blood pressure during the day and night than in the placebo group.

The inclusion of adaptol in the treatment regimen increased the severity of the lipid-lowering effect of the combination of statins and adaptol compared to statins. According to L.A. Lapshina, P.G. Kravchun, O.S. Shevchenko (2008), correction of psychopathological manifestations and oxidative stress by adaptol in patients who have suffered a myocardial infarction is evidence of the specific effect of adaptol in correcting the lipid composition of the blood and seems especially important in patients who have suffered an acute MI.

Compared with standard therapy for patients with post-infarction cardiosclerosis, the addition of adaptol to it led to a more pronounced positive effect on the processes of free radical oxidation (decrease in pro-oxidant and increase in antioxidant activity). V.N. Kovalenko et al. (2006) showed that the addition of adaptol to the complex therapy of hypertension and neurocirculatory dystonia contributed to the improvement of heart rate variability parameters with a decrease in the activity of the sympathetic division of the autonomic nervous system, restoring its balance with normalization of the regulation of heart activity.

In the work of L.M. Vasilets et al. [2] studied the structure of heart rhythm disturbances and the features of temporal analysis of heart rate variability in patients with the syndrome and phenomenon of premature excitation of the ventricles. It was shown that the use of adaptol in a dose of 500 mg 2 times a day for 60 days against the background of antiarrhythmic therapy with amiodarone helped to reduce autonomic imbalance and reduced the arrhythmogenic readiness of the myocardium.

The antihyperlipidemic, antioxidant, and anti-ischemic effects of the drug obtained experimentally and clinically cannot in any way be due only to the studied central mechanisms of its action.

And if the antioxidant effect of the drug can also be explained by the fact that the drug molecule contains two methylated urea fragments, and urea is considered as a reference antioxidant, then the antihyperlipidemic and antianginal effects of the drug cannot be associated only with its central and antioxidant action. In this regard, it is of particular interest to directly study the mechanisms of the drug’s influence on lipid metabolism, the peroxidation system, and especially coronary blood flow, both experimentally and in clinical practice, especially taking into account the effect of the drug on the chemical activity of water.

There is evidence that extremely high-frequency (EHF; millimeter waves) irradiation stimulates cellular receptors of a protein nature due to the activation of the aqueous component of the extracellular fluid. At the same time, the fraction of mobile, chemically active H2O molecules increases. The introduction of certain low-molecular substances into the biological environment that destabilize the structure of water can simulate the effects of EHF irradiation. This effect is inherent in urea. Under its influence, the generation of a fraction of mobile water molecules in solution and, along with this, the depletion of a fraction of bulk water not included in the fraction of mobile molecules was revealed. Depletion of the bulk water fraction was correlated with the instability of proteins such as chymotrypsinogen and serum albumin (denaturation). The authors believe that since the unfolding of the protein globule is preceded by an increase in intraglobular mobility, the denaturation effect manifests both direct and indirect effects of urea on protein dynamics through the destruction of the water structure.

The structural determinant of the urea fragment, which is responsible for its ability to generate mobile water molecules, has been established: the presence of two close and parallel N–H bonds.

Similar properties were found in mebicarum [12]. Urea and mebicarum activate water as a nucleophilic reagent. An increase in the chemical activity of water is associated with the destruction of the structure of water, i.e. with an increase in the proportion of rotator molecules. Most likely, all this determines the unusually wide range of pharmaceutical activity of the anxiolytic mebicarum without its inclusion in metabolism and in the absence of specific receptors.

The above can largely shed light on the unique, multifaceted spectrum of clinical effectiveness of adaptol and proves the need for a deeper study and detailed mechanisms of action of the drug in such various pathological processes both in the clinic and in experiments.

OLFA: calm, only calm!

ADAPTOL and NOOFEN have a wide range of indications and can be prescribed for the prevention, correction and treatment of a number of psychosomatic conditions. At the same time, they are well tolerated and can be used in patients of any age, including children and the elderly. Both drugs are included in the List of medicines dispensed without a prescription from pharmacies and their structural divisions, approved by the Ministry of Health of Ukraine.

ADAPTOL belongs to the so-called daytime tranquilizers. The drug has moderate tranquilizing activity, eliminates or reduces the severity of restlessness, anxiety, fear, internal emotional tension and irritability. At the same time, it does not cause muscle relaxation or impaired coordination of movements, does not affect mental and physical performance, so it can be used when engaging in any type of activity. Although ADAPTOL does not have a hypnotic effect, it enhances the effect of hypnotics and improves sleep in case of sleep disturbances.

The drug has extremely low toxicity, since it is close in chemical composition to the natural metabolites of the human body, does not cause addiction, addiction, or withdrawal symptoms; it has a favorable safety profile.

ADAPTOL reduces the influence of the sympathetic part of the autonomic nervous system, which makes it indispensable in the treatment of vegetative-vascular dystonia, chronic fatigue syndrome, and premenstrual syndrome.

The antihypoxic and antioxidant properties of the drug make it possible to use ADAPTOL for injuries, ischemic and hypoxic damage to organs and systems of various origins. The adaptogenic effect of the drug allows you to correct the state of the nervous system when the body’s regulatory systems are weakened or disrupted, and protects against the effects of stress.

Indications for the use of ADAPTOLA are quite broad - these are neuroses and neurosis-like states that occur with symptoms of irritability, emotional instability, anxiety and fear. In the clinic of internal diseases, ADAPTOL is indicated for cardialgia of various origins, not associated with coronary heart disease. The drug is also prescribed to improve the tolerability of neuroleptics and tranquilizers in order to eliminate the somatovegetative and neurological side effects they cause. Since the active substance of ADAPTOLA is practically chemically inert, it can be combined with any other medicines. In particular, ADAPTOL is used in combination with antipsychotics, tranquilizers (benzodiazepines), hypnotics, antidepressants and psychostimulants in the complex treatment of various maladaptive conditions or intoxication caused by these drugs.

An important property of ADAPTOLA is the ability to eliminate or reduce the severity of nicotine withdrawal, as a result of which the drug can be used to treat patients with nicotine addiction.

Another over-the-counter drug from , which corrects the psycho-emotional and vegetative spheres - NOOFEN - has a wider range of applications. It has a nootropic, antiasthenic, tranquilizing, neuroprotective and vegetative stabilizing effect, and also has an analgesic effect.

NOOFEN improves GABAergic neurotransmitter transmission and functional characteristics of neurons, increases energy resources and activates metabolic processes, has an antihypoxic effect, thereby improving memory, increasing learning ability, intellectual activity and brain resistance to harmful influences, and stimulating physical performance. The activating effect of NOOPHEN is especially pronounced in children and elderly patients. NOOFEN reduces the severity of asthenia and vasovegetative symptoms, including headache, sleep disturbances, irritability, and mood swings.

Due to the normalization of the neurotransmitter system, NOOFEN has antiepileptic activity and is used in the complex treatment of epilepsy and epileptic equivalents, as well as parkinsonism.

The drug is low toxic because its chemical structure is close to the natural neurotransmitter - aminobutyric acid, while at the same time it does not affect choline and adrenergic receptors. The effect of using NOOPHEN occurs within the first hours of administration, which allows it to be used for the prevention and treatment of sea and airborne illnesses, stress conditions before operations or painful diagnostic interventions.

Indications for the use of NOOPHEN are a decrease in intellectual and emotional activity, concentration, memory impairment, asthenic and anxiety-neurotic conditions, hypertensive encephalopathy, stroke, Meniere's disease, dizziness associated with dysfunction of the vestibular apparatus of various origins, states of anxious arousal and night restlessness in vascular and senile psychoses. NOOFEN is used for menopausal syndrome. In pediatric practice, the drug is used for the treatment of logoneurosis, tics and enuresis.

The ability to prolong and enhance the effect of hypnotics, narcotics, neuroleptics and anticonvulsants allowed the use of NOOFEN in combination with these drugs for mutual potentiation of therapeutic effects.

In chronic alcoholism, NOOFEN is indicated as an adjuvant for the relief of psychopathological and somatovegetative disorders during withdrawal syndrome, and can be used along with generally accepted detoxification agents for alcoholic predelirious and delirious states.

When used after a traumatic brain injury, NOOFEN increases the number of mitochondria in the cells of perifocal tissues and improves the bioenergetics of the brain. For neurogenic disorders of the heart and stomach, the drug normalizes the processes of lipid peroxidation. Under the influence of NOOPHEN, indicators of higher nervous activity (attention, memory, speed and accuracy of sensory-motor reactions) improve.

Due to the high effectiveness of the drugs ADAPTOL and NOOFEN, their wide spectrum of action, the rapid onset of the clinical effect, combined with a high level of safety, the absence of side effects, good tolerability, the possibility of use in both children and the elderly and senile, both drugs were allowed to be dispensed from pharmacies without a doctor's prescription. o

Anna Proskurina