Neuromidin, 5 mg/ml, solution for intramuscular and subcutaneous administration, 1 ml, 10 pcs.

Nosological classification (ICD-10)

• F09 Organic or symptomatic mental disorder, unspecified
• G12.2 Motor neuron disease
• G37.9 Demyelinating disease of the central nervous system, unspecified
• G58 Other mononeuropathies
• G61 Inflammatory polyneuropathy
• G62 Other polyneuropathies
• G62.9 Polyneuropathy, unspecified
• G70 Myasthenia gravis and other neuromuscular junction disorders
• G92 Toxic encephalopathy
• G96.8 Other specified disorders of the central nervous system
• G96.9 Damage to the central nervous system, unspecified
• K59.8.0* Intestinal atony
• M79.2 Neuralgia and neuritis, unspecified

According to epidemiological studies, 3-10% of the population over 18 years of age in different regions of the world are susceptible to chronic alcohol abuse [17, 27, 29]. In the Russian Federation, the problem of excessive alcohol consumption is also very acute; alcoholism ranks third among the causes of mortality in Russia. Therefore, the therapy of acute alcohol poisoning, as well as the treatment and prevention of motor, sensory, and cognitive disorders in chronic alcohol intoxication are urgent tasks facing modern medicine [1, 4, 13].

The most common complication of chronic alcohol intoxication is the development of alcoholic polyneuropathy, which occurs 5 times more often than encephalopathy [2, 14]. Nevertheless, the study of the latter, especially in the aspect of correction of alcoholic damage to the central nervous system, is extremely important, since in many cases the disease is very severe and in almost all patients significantly reduces the quality of life [5, 9, 15].

The pathogenetic mechanisms of damage to nervous tissue during alcoholism are quite complex. It has been proven that ethyl alcohol is membrane toxic, and as a result of its systematic use, the gray and white matter of the brain is damaged, which is accompanied by the loss of myelin fibers and neurons, the gradual development of brain atrophy, degradation of the microstructures of the corpus callosum, a decrease in neuronal and glial markers, which creates the basis for neuropsychiatric disorders [10, 16, 20]. One of the factors causing damage to nervous tissue during alcoholism is a deficiency of B vitamins, primarily thiamine. Under the influence of alcohol, the absorption of thiamine in the small intestine decreases, the supply of thiamine in the liver decreases, and its intracellular phosphorylation is disrupted. As a result, there is a decrease in the incorporation of lipids into myelin, intracellular accumulation of calcium, and disruption of the biosynthesis and metabolism of mediators, which enhances the neurotoxic effect of ethanol and its metabolites [21, 28]. The direct neurotoxic effect of ethanol and its derivatives on neurons develops through the mechanism of glutamate neurotoxicity due to a decrease in the production of neurofilament protein and disruption of fast axonal transport [22]. Clinical studies showing a dose-dependent effect between the amount of ethanol taken and the severity of damage to the nervous system confirm the presence of a direct toxic effect of alcohol [25, 26].

The multiple effects of ethanol on the central nervous system are also associated with its ability to increase the permeability of the blood-brain barrier (BBB) ​​to low molecular weight compounds. This also applies to the main neurochemical systems of the brain (dopaminergic, serotonergic, noradrenergic, cholinergic and GABAergic), and the corresponding neurotransmitters, the functions of which may be impaired under the influence of alcohol. We can only note that relatively little data has been accumulated on the role of acetylcholine in the development of alcoholism, although it is one of the main neurotransmitters of the central nervous system.

Currently, there are a fairly large number of drugs that have a secondary neuroprotective effect, many of which are cholinergic drugs [24].

Neuromidin (ipidacrine) occupies a special place among cholinergic drugs. The mechanism of its action is associated with the blockade of cholinesterase activity in the brain and neuromuscular synapse, as well as with the selective blockade of membrane potassium channels. It is the effect of ipidacrine (neuromidin) on the transport of potassium ions that underlies the action of the drug. Blockade of potassium channels causes an extension of the period of excitation in the presynaptic fiber during the passage of a nerve impulse, ensures the release of large quantities of acetylcholine into the synaptic cleft and thus increases the working concentration of the transmitter near the postsynaptic membrane [8, 18].

In addition to acetylcholinesterase, neuromidin can also inhibit another enzyme that destroys acetylcholine, butyrylcholinesterase. Interest in this enzyme is due to the fact that butyrylcholinesterase in Alzheimer's disease is detected in neurofibrillary tangles and senile plaques, and as this disease progresses, acetylcholinesterase activity decreases in certain areas of the brain, while butyrylcholinesterase activity increases. According to a number of experimental and clinical studies [19, 23], inhibition of butyrylcholinesterase is accompanied by an improvement in visuospatial functions, memory and learning ability.

The purpose of this study was to evaluate the effectiveness and safety of the drug Neuromidin in patients with alcoholic encephalopathy.

Material and methods

An open comparative controlled study was conducted. The formation of groups of patients was carried out based on the following inclusion criteria: the presence of a neurological deficit, an alcohol history and a documented diagnosis of toxic encephalopathy of alcoholic nature.

The study included 40 patients of both sexes aged from 30 to 60 years. All of them had higher specialized education and were engaged in intellectual work.

The main group of patients consisted of 20 people. They were prescribed treatment with neuromidin: a solution of neuromidin at a dose of 15 mg was administered intramuscularly for 10 days, then neuromidin was given in tablets of 20 mg 3 times a day for 2 months. Therapy with neuromidin was carried out against the background of treatment with vasoactive drugs and antioxidants.

The comparison group included 20 people who received only vasoactive and antioxidant therapy. Patients in the control and main groups were excluded from taking drugs with nootropic effects and B vitamins.

Each patient received full information about the drug and its properties, the purpose and principles of the study, and gave written informed consent to participate in the study.

The criteria for excluding patients from the study were: severe condition of the patient, which makes it difficult to assess the clinical effectiveness of the drug; hypersensitivity to neuromidin; the presence of severe concomitant pathology that complicates the interpretation of treatment results (malignant neoplasms, acute cerebrovascular accident, epilepsy, congestive heart failure - NYHA class II-IV, renal failure - creatinine more than 0.18 mmol/l, fever), the patient’s inability to understand the study procedure or inability to visit a doctor after treatment.

Evaluation of the effectiveness of treatment was based on the neurological status of the patient before and after treatment. At the same time, attention was paid to speech disorders, disorders of praxis and gnosis, oculomotor disorders, bulbar disorders, the presence of pseudobulbar syndrome, manifestations of motor deficits, sensitivity disorders, extrapyramidal disorders, and motor coordination disorders.

To assess the state of cognitive functions before and after treatment, neuropsychological testing was performed using the Beck Depression Scale, the Schulte table, and the Luria “10 Words” test; A short scale for assessing mental status was also used - MMSE (Mini Mental State Examination) [3].

The assessment of the quality of life was carried out on the basis of the SF-36 questionnaire (Russian version created and recommended by the International Center for Quality of Life Research), which provides a quantitative determination of the quality of life on several scales of the physical and mental subjective well-being of patients (maximum satisfaction corresponds to a score of 100 points) [12 ].

The reliability of changes in test results according to the Beck scales, MMSE, SF-36 questionnaire, and cognitive evoked potential studies were assessed using static methods [6]. To compare observations by ordinal in the main group treated with neuromidin before and after treatment, the Wilcoxon test (W) was used.

Before starting therapy, biochemical blood parameters such as ALT, AST, bilirubin, creatinine, glucose, and cholesterol were assessed. To exclude heart rhythm disturbances, coronary insufficiency, and signs of myocardial ischemia, electrocardiography was performed before treatment.

Neuroimaging methods included computed tomography or magnetic resonance imaging (CT or MRI) of the brain. In addition, cognitive evoked potentials (EPs) were studied before and after treatment [7, 11]. The main indicator in this case was the P300 wave - its presence, latent period and amplitude. An increase in latency and a decrease in P300 amplitude were considered as indicators of cognitive impairment.

Results and discussion

The most common complaints of those examined were impaired attention - in 32 (80%) patients, forgetfulness - in 28 (70%), increased anxiety - in 14 (35%), recurrent headaches - in 33 (82.5%), dizziness - in 17 (42.5%), unsteadiness of gait - in 12 (30%), numbness of hands and feet - in 8 (20%), trembling of hands - in 23 (57.5%).

During a neurological examination of patients in both groups, the following disorders were revealed: installation horizontal nystagmus at the extreme abduction of the eyeballs - in 25 (62.5%) patients, 17 of whom belonged to the main group and 8 to the control; decreased carporadial and Achilles reflexes - in 15 (37.5%) patients, 9 from the main group and 6 from the control group; diffuse decrease in muscle strength - in 5 (25%) patients of the main group; hypoesthesia of the “gloves” and “socks” type - in 5 (25%) people from the main group; intention tremor of varying degrees of intensity when performing the finger-nose test and/or ataxia when performing the heel-knee test - in 29 (72.5%) patients - 17 from the main group and 12 from the control; instability in the Romberg position - in 12 (30%), 9 from the main group and 3 from the control; symptoms of oral automatism - in 3 (15%) patients of the main group. Pathological foot and hand symptoms were not observed in either the study or control groups.

After a course of neuromidin therapy, a significant regression of subjective sensations and an improvement in the neurological status in the main group were observed in the following indicators: a decrease in the intensity of nystagmus - in 13 (65%) patients, a revival of carporadial and Achilles reflexes - in 4 (20%), an increase in muscle strength to 5 points - in 5 (25%), reduction in the intensity of hypoesthesia in the arms and legs - in 3 (15%), improvement in the performance of coordination tests in 14 (70%).

In the control group, no positive dynamics in the neurological status were observed; In 3 patients, an increase in cerebellar symptoms was detected (increased intention tremor, instability when walking, deterioration in handwriting).

The positive effect of neuromidin therapy on cognitive functions was evidenced by a significant increase in the total score on the MMSE scale by the end of the course of therapy in the main group, while moderate cognitive deficits continued to be recorded in the control group (Table 1).

When analyzing the results of MMSE indicators after a course of therapy, a significantly significant improvement was revealed in patients of the main group: W=50 (with W critical = 44; p=0.05).

The data obtained are consistent with the results obtained earlier by M.S. Golovkova et al. [8] in patients with vascular cognitive impairment.

Positive therapeutic dynamics in patients of the main group were also revealed when assessing the severity of depressive disorders on the Beck scale (Table 2).

After treatment with neuromidin, there was a significant improvement in the main group of patients: W = 68 (with W critical = 58; p = 0.02).

Quality of life was analyzed using the SF-36 questionnaire on the following scales: physical functioning (PF), role (physical) functioning (RP), pain intensity (BP), general health (GH), vitality (VT), social functioning (SF) , role-emotional functioning (RE), mental health (MH) [12]. In the main group, a significantly significant improvement (p<0.05) was recorded in both physical (PF, RP, VP, GH) and mental (VT, SF, RE, MH) components of health. In the control group, a significantly significant (p<0.05) improvement was observed only on the GH scale (Table 3).

A study using the SF-36 quality of life questionnaire thus revealed an improvement in the quality of life in the main group of patients on all scales. The most pronounced increase in indicators was noted on the scales of physical functioning (PF), general health (GH), emotional functioning (RE), and mental health (MH). An increase in these indicators may indicate an improvement in the patient's physical condition during activities such as walking, climbing stairs, etc., as well as increased performance and activity in performing normal daily duties and increased social activity (communication).

When assessing the indicators of cognitive EP, namely the latent period and amplitude of the P300 wave, in the main group, positive dynamics were also noted in the form of a decrease in the latent period and an increase in amplitude, while in the control group no significant changes in these indicators were observed (Table 4).

When studying repeated measurements of qualitative signs (latent period of P300) in the main group, the McNemar criterion was used (χ2 = 10.74; p = 0.01), which indicates a significantly significant positive effect of neuromidin on the latent period of P300 waves.

CT and MRI of the brain in all patients of the main group and in 11 people from the control group revealed the following changes: atrophy of the brain substance, more pronounced in the frontal lobes and cerebellum, deepening of the Sylvian fissures and interhemispheric spaces, slight expansion of the lateral ventricles. These changes did not correlate with the characteristics of the P300 wave of cognitive EP, impairments in memory, attention and performance of patients.

When making a general assessment of the results obtained, one must take into account that the patients examined were engaged in intellectual work, i.e. with fairly high social adaptation. For a more accurate interpretation, further observations on a larger group of patients and analysis depending on the types of drinks consumed and the duration of the disease are required.

During treatment with Neuromidin, no adverse events or side effects of the drug were identified.

Thus, a course of treatment with neuromidin (10 days neuromidin 15 mg intramuscularly, then neuromidin tablets 20 mg 3 times a day for 2 months) in patients with alcoholic encephalopathy leads to an improvement in the clinical condition of patients and quality of life indicators, and is also safe for the patient .

When treated with neuromidin in the dosages used, patients showed an improvement in cognitive functions both according to the results of neuropsychological testing and according to the study of cognitive EP (P300 waves).

Compound

Pharmacodynamics

Neuromidin® has a direct stimulating effect on the conduction of impulses along nerve fibers, interneuronal and neuromuscular synapses of the central nervous system and the peripheral nervous system. The pharmacological action of Neuromidin® is based on a combination of two mechanisms of action: blockade of potassium channels in the membrane of neurons and muscle cells; reversible inhibition of cholinesterase at synapses.

Neuromidin® enhances the effect on smooth muscles of not only acetylcholine, but also adrenaline, serotonin, histamine and oxytocin.

Neuromidin® has the following pharmacological effects:

– improves and stimulates impulse conduction in the nervous system and neuromuscular transmission;

- enhances the contractility of smooth muscle organs under the influence of agonists of acetylcholine, adrenaline, serotonin, histamine and oxytocin receptors, with the exception of potassium chloride;

- improves memory, inhibits the progressive course of dementia.

In preclinical studies, Neuromidin® did not have teratogenic, embryotoxic, mutagenic, carcinogenic or immunotoxic effects, and did not affect the endocrine system.

Buy Neuromidin solution intravenously and intramuscularly 5mg/ml 1ml No. 10 in pharmacies

Instructions for use

Neuromidin solution IV and IM 5 mg/ml 1 ml No. 10

Dosage forms injection solution 5 mg/ml 1 ml Synonyms Axamon Ipigrix Group Cholinesterase inhibitors International nonproprietary name Ipidacrine Composition Active substance: Ipidacrine. Manufacturers: Olainfarm JSC (Latvia), Olainfarm JSC, packaged Sopharma JSC (Latvia), Olainfarm Olainsky HFZ (Latvia) Pharmacological action Reversibly inhibits cholinesterase, stimulates impulse conduction in neuromuscular synapses and in the central nervous system due to blockade of potassium channels of the excitable membrane. Restores and stimulates neuromuscular transmission (including in the peripheral nervous system), enhances the contractility of smooth muscle organs, moderately stimulates the central nervous system, improves memory and learning. Does not have teratogenic, embryotoxic, mutagenic, carcinogenic, allergenic, or immunotoxic effects. Does not affect the endocrine system. The drug penetrates well into all tissues of the body, increases the tone of the uterus and can cause premature birth. The drug can be used for weak labor. After oral administration, it is quickly absorbed. It is excreted through the kidneys and through the gastrointestinal tract, mainly in the form of metabolites. Side effects: Dizziness, bradycardia (can be eliminated with m-anticholinergic blockers), hypersalivation (can be eliminated with m-anticholinergic blockers), nausea, vomiting, itching, rash. Indications for use Diseases of the peripheral nervous system in adults (neuritis, polyneuritis, polyneuropathy, polyradiculoneuropathy, myasthenia gravis); bulbar palsy and paresis, organic lesions of the central nervous system, accompanied by nervous disorders (recovery period); demyelinating diseases (complex therapy), intestinal atony. Contraindications Hypersensitivity, epilepsy, extrapyramidal disorders, severe bradycardia, angina pectoris, bronchial asthma, vestibular disorders, gastric ulcer in the acute stage, pregnancy, breastfeeding. Overdose Treatment: prescription of m-anticholinergics, incl. atropine, cyclodol, etc. Interaction Strengthens the sedative effect of central nervous system depressants. M-cholinomimetics and other cholinesterase inhibitors increase the effect and side effects (the risk of a cholinergic crisis increases, especially in patients with myasthenia gravis). Beta-blockers cause bradycardia if they were used before treatment with Neuromidin. When used simultaneously with alcohol, adverse side effects may increase. Special instructions The drug increases the muscle tone of the uterus and can cause premature labor. Caution should be used for stomach ulcers, thyrotoxicosis, and diseases of the cardiovascular system. The drug penetrates well into tissues and organs, incl. brain and may have a sedative effect. Care should be taken when working with machinery. During treatment you should not drink alcohol. Storage conditions List A. In a place protected from light, at a temperature not exceeding 25 °C.

Pharmacokinetics

After oral administration, intramuscular and subcutaneous administration, it is rapidly absorbed. Cmax in blood plasma is achieved 1 hour after oral administration and 25–30 minutes after intramuscular or subcutaneous administration. Binding to blood plasma proteins is 40–50% of the active substance. It quickly enters the tissues, the half-life of distribution is 40 minutes. Metabolized in the liver. It is excreted through the kidneys (mainly by tubular secretion and only 1/3 by glomerular filtration) and extrarenally (through the gastrointestinal tract). T1/2 of Neuromidin® when administered parenterally is 2–3 hours. After parenteral administration, 34.8% of the drug dose is excreted unchanged in the urine.

Contraindications

hypersensitivity to any of the components of the drug;

epilepsy;

extrapyramidal diseases with hyperkinesis;

angina pectoris;

severe bradycardia;

bronchial asthma;

mechanical obstruction of the intestine or urinary tract;

vestibular disorders;

peptic ulcer of the stomach or duodenum in the acute stage;

pregnancy (the drug increases the tone of the uterus);

lactation period;

children under 18 years of age (no systematic data on use).

With caution: for gastric and duodenal ulcers, thyrotoxicosis, cardiovascular diseases, as well as for patients with a history of obstructive diseases of the respiratory system or acute respiratory diseases.

Additionally for tablets

With caution: with lactase deficiency, lactose intolerance, lactose/isomaltose malabsorption syndrome, because the drug contains lactose.

Neuromidin 20 mg No. 50 tablet.

Instructions for medical use of the drug NEIROMIDIN® Trade name Neuromidin® International nonproprietary name Ipidacrine Dosage form Tablets 20 mg Composition One tablet contains the active substance: ipidacrine hydrochloride 20 mg, excipients: lactose monohydrate, potato starch, calcium stearate. Description White or almost white, flat-cylindrical tablets with a bevel. Pharmacotherapeutic group Psychoanaleptics. Cholinesterase inhibitors. Ipidacrine. ATC code N06DA05 Pharmacological properties Pharmacokinetics After oral administration, ipidacrine hydrochloride is rapidly absorbed from the gastrointestinal tract. Absorption occurs mainly from the duodenum, and to a lesser extent from the small intestine. The maximum concentration in blood plasma is reached after an hour. About 40-55% of the active substance binds to blood plasma proteins. The active substance quickly penetrates from the blood into the tissues and overcomes the blood-brain barrier. After achieving equilibrium distribution, about 2% of the active substance remains in the blood plasma. Mainly metabolized in the liver by hydroxylation. Metabolites retain the same action profile, but the severity of their effects is much weaker. Elimination occurs renal and extrarenally, excretion in the urine by tubular secretion predominates, and only 1/3 of the dose is excreted by glomerular filtration. The terminal half-life is 2-3 hours. When administered orally, only 3.7% of the dose is excreted unchanged in the urine. Does not cumulate. Pharmacodynamics Neuromidin® is a reversible cholinesterase inhibitor. The drug directly stimulates the conduction of impulses in the neuromuscular synapse and in the central nervous system due to the blockade of potassium channels in the membrane. Neuromidin® enhances the effect on smooth muscles of not only acetylcholine, but also adrenaline, serotonin, histamine and oxytocin. Neuromidin® has the following pharmacological effects: · improves and stimulates neuromuscular transmission; · restores the conduction of impulses in the peripheral nervous system, impaired due to various factors (trauma, inflammation, exposure to local anesthetics, some antibiotics, potassium chloride, etc.); · increases the contractility of smooth muscle organs under the influence of all agonists, with the exception of potassium chloride; · moderately stimulates the central nervous system in combination with the manifestation of individual sedative effects; · improves memory. Indications for use As part of complex therapy - diseases of the peripheral nervous system (neuritis, polyneuritis, polyneuropathy, polyradiculoneuropathy, myasthenia gravis and myasthenic syndrome of various etiologies); - bulbar paralysis and paresis; — during the recovery period after organic lesions of the central nervous system, accompanied by motor disorders; - demyelinating diseases of the nervous system (including multiple sclerosis); — memory impairments of various origins (Alzheimer’s disease, other forms of senile dementia); - intestinal atony. Directions for use and dosage: Inside. Doses and duration of treatment are determined individually depending on the severity of the disease. The highest single dose is 40 mg, the maximum daily dose is 200 mg. For neuritis: 20 mg 2-3 times a day. The course of treatment for acute neuritis is from 10-15 days, for chronic neuritis - up to 20-30 days. If necessary, the course of treatment is repeated 2-3 times with an interval of 2-4 weeks until a therapeutic effect is achieved; For polyradiculoneuropathy: 20 mg 2-3 times a day for 30-40 days. The course of treatment is repeated many times with a break of 1-2 months until a therapeutic effect is achieved; For myasthenia gravis and myasthenic syndrome: 10-20 mg (1/2 - 1 tablet) 1-3 times a day. The course of treatment is from 1 to 2 months. If necessary, the course of treatment can be repeated several times with a break between courses of 1-2 months. Recovery period for organic lesions of the central nervous system, accompanied by motor disorders: 20 mg 3 times a day for 60 days. For demyelinating diseases of the nervous system (including multiple sclerosis): 20 mg 3-5 times a day for 60 days 2-3 times a year. For memory impairment of various origins (including Alzheimer's disease): 20 mg 2-3 times a day. The duration of treatment is from 4 months to 1 year. To prevent myasthenic crises in severe disorders of neuromuscular conduction, 1-2 ml (15-30 mg) Neuromidin® 1.5% solution for injection is administered intramuscularly or subcutaneously for a period determined by the doctor, then treatment is continued with the tablet form of the drug and the dose can be increased to 20-40 mg 5 times a day, the course of treatment is determined by the doctor and depends on the dynamics of the clinical picture. The maximum daily dose is 200 mg. For intestinal atony: 20 mg 2-3 times a day for 1-2 weeks. Side effects Often - hypersalivation, nausea - palpitations, bradycardia - increased sweating Less often - increased secretion of bronchial secretions - after using high doses - dizziness, headache, weakness, drowsiness, muscle cramps, allergic reactions (skin itching, rash), vomiting Rarely - epigastric pain, diarrhea Not known (cannot be determined from the available data) - bronchospasm Salivation and bradycardia can be reduced with m-anticholinergic drugs (atropine, etc.). In these cases, reduce the dose or interrupt the drug for a short time (for 1-2 days). Contraindications - hypersensitivity to ipidacrine or to the excipients of the drug - epilepsy - extrapyramidal diseases with hyperkinesis - angina pectoris - severe bradycardia - bronchial asthma - blockage of the intestines or urinary tract - tendency to vestibular disorders - peptic ulcer of the stomach or duodenum in the acute stage - pregnancy and breastfeeding - children and adolescents up to 18 years of age (adequate studies to study the safety of the drug in children have not been conducted). Drug interactions The presence of a sedative effect in the spectrum of activity of Neuromidin® leads to some potentiation of the effects of hypnotics (hexenal, chloral hydrate) in large doses, while in small doses Neuromidin® either does not affect or weakens the effect of hypnotics. The action and side effects are enhanced when used together with other cholinesterase inhibitors and m-cholinomimetic drugs. In patients with Myasthenia gravis, the risk of developing a cholinergic crisis increases when using other cholinomimetic drugs. The risk of developing bradycardia increases if b-blockers were used before starting treatment with Neuromidin®. Cerebrolysin increases the effectiveness of the drug. Neuromidin® weakens the effect of local anesthetics and antibiotics. Alcohol increases the side effects of the drug. Special instructions If you miss a regular dose, take the drug as soon as you remember, but skip it if it is almost time for the next dose. Never take a double dose! Prescribe with caution for gastric and duodenal ulcers, thyrotoxicosis, diseases of the cardiovascular system, as well as for patients with a history of respiratory tract diseases or acute respiratory tract diseases. The drug contains lactose. Should not be used in patients with rare congenital galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption. Features of the effect of the drug on the ability to drive a vehicle or potentially dangerous mechanisms Neuromidin® may have a sedative effect, therefore, persons who experience side effects from the central nervous system, for example, drowsiness, should refrain from driving. Overdose In severe overdose, a “cholinergic crisis” may develop with symptoms: bronchospasm, lacrimation of the eyes, increased sweating, constriction of the pupils, nystagmus, spontaneous defecation and urination, vomiting, bradycardia, heart block, arrhythmias, hypotension, restlessness, anxiety, agitation, feelings of fear , ataxia, convulsions, coma, slurred speech, drowsiness and weakness. Symptoms may be mild. Treatment: drug withdrawal, gastric lavage, symptomatic therapy, using m-anticholinergic drugs: atropine, cyclodol or metacin, which reduce the severity of overdose symptoms. Release form and packaging 10 tablets in a blister pack made of polyvinyl chloride film and aluminum foil. 5 contour packages along with instructions for medical use in the state and Russian languages ​​in a cardboard pack. Storage conditions Store in a dry place, protected from light, at a temperature not exceeding 25 °C. Keep out of the reach of children! Shelf life: 5 years Do not use after the expiration date indicated on the package. Conditions for dispensing from pharmacies According to prescription Manufacturer: OLAINPHARM JSC. Address: st. Rupnicu 5, Olaine, LV-2114, Latvia. Address of the organization receiving claims from consumers regarding product quality on the territory of the Republic of Kazakhstan: 050009 Almaty, Abay Ave. 151/115, office 807, phone/fax 007 727 333 46 52, E-mail

Side effects

Caused by stimulation of m-cholinergic receptors: salivation, increased sweating, palpitations, nausea, diarrhea, jaundice, bradycardia, epigastric pain, increased secretion of bronchial secretions, bronchospasm, convulsions. Salivation and bradycardia can be reduced with m-anticholinergic drugs (atropine, etc.). Increased uterine tone, allergic skin reactions.

Rarely (after using higher doses), dizziness, headache, chest pain, vomiting, general weakness, drowsiness, and skin reactions (itching, rash) were observed. In these cases, reduce the dose or interrupt the drug for a short time (for 1–2 days). These side effects are observed in less than 10% of patients.

Neuromidin 20 mg 50 pcs. pills

pharmachologic effect

Cholinesterase inhibitor.

Composition and release form Neuromidin 20 mg 50 pcs. pills

Tablets - 1 tablet:

• active ingredient: ipidacrine hydrochloride monohydrate (in terms of ipidacrine hydrochloride) 20 mg;
• excipients: lactose monohydrate 65.0 mg, potato starch 14.0 mg, calcium stearate 1.0 mg.

Tablets, 20 mg.

10 tablets in a blister pack made of polyvinyl chloride film and aluminum foil.

5 blister packs along with instructions for use are placed in a cardboard pack.

Description of the dosage form

Round, flat-cylindrical, white tablets with a chamfer.

Directions for use and doses

Inside.

Doses and duration of treatment are determined individually depending on the severity of the disease.

Diseases of the peripheral nervous system: mono- and polyneuropathy, polyradiculopathy, myasthenia gravis and myasthenic syndrome of various etiologies - 10-20 mg (0.5-1 tablet) 1-3 times a day. The course of treatment is from one to two months. If necessary, the course of treatment can be repeated several times with a break between courses of 1-2 months.

To prevent myasthenic crises, in case of severe disorders of neuromuscular conduction, 1-2 ml (15-30 mg) Neuromidin® 1.5% injection solution is administered parenterally for a short time, then treatment is continued with Neuromidin® tablets, the dose can be increased to 20-40 mg (1-2 tablets) 5 times a day.

Diseases of the central nervous system: bulbar paralysis and paresis, the recovery period of organic lesions of the central nervous system (traumatic, vascular and other origins), accompanied by motor and/or cognitive impairment - 10-20 mg (0.5-1 tablet) 2-3 times in a day. The course of treatment is from 2 to 6 months. If necessary, the course of treatment is repeated.

Treatment and prevention of intestinal atony: 20 mg (one tablet) 2-3 times a day for 1-2 weeks.

If the next dose was not taken on time, then it is not taken additionally. The maximum daily dose is 200 mg.

Pharmacodynamics

Neuromidin® has a direct stimulating effect on the conduction of impulses along nerve fibers, interneuronal and neuromuscular synapses of the peripheral and central nervous system.

The pharmacological action of Neuromidin® is based on a combination of two mechanisms of action:

• blockade of potassium channels in the membrane of neurons and muscle cells;
• reversible inhibition of cholinesterase at synapses.

Neuromidin® enhances the effect on smooth muscles of not only acetylcholine, but also adrenaline, serotonin, histamine and oxytocin.

Neuromidin® has the following pharmacological effects:

• improves and stimulates impulse conduction in the nervous system and neuromuscular transmission;
• enhances the contractility of smooth muscle organs under the influence of agonists of acetylcholine, adrenaline, serotonin, histamine and oxytocin receptors, with the exception of potassium chloride;
• improves memory, inhibits the progression of dementia.

In preclinical studies, Neuromidin® did not have teratogenic, embryotoxic, mutagenic, carcinogenic or immunotoxic effects, and did not affect the endocrine system.

Pharmacokinetics

After oral administration, the drug is quickly absorbed from the gastrointestinal tract. The maximum concentration in blood plasma is reached after one hour. 40-50% of the active substance binds to blood plasma proteins. Neuromidin® quickly enters tissues, the half-life of distribution is 40 minutes. Metabolized in the liver. Excretion is carried out through the kidneys, as well as extrarenally (through the gastrointestinal tract). Excretion of the drug Neuromidin® by the kidneys occurs mainly by tubular secretion, and only 1/3 of the dose is excreted by glomerular filtration.

Indications for use Neuromidin 20 mg 50 pcs. pills

Diseases of the peripheral nervous system: mono- and polyneuropathy, polyradiculopathy, myasthenia gravis and myasthenic syndrome of various etiologies.

Diseases of the central nervous system: bulbar palsy and paresis; recovery period of organic lesions of the central nervous system, accompanied by motor and/or cognitive impairment.

Treatment and prevention of intestinal atony.

Contraindications

Hypersensitivity to any of the components of the drug, epilepsy, extrapyramidal diseases with hyperkinesis, angina pectoris and severe bradycardia, bronchial asthma, mechanical obstruction of the intestine or urinary tract, vestibular disorders, gastric or duodenal ulcers in the acute stage, pregnancy (the drug increases the tone of the uterus) and lactation period.

Children under 18 years of age (no systematic data on use).

With caution: for gastric and duodenal ulcers, thyrotoxicosis, diseases of the cardiovascular system, as well as for patients with a history of obstructive diseases of the respiratory system or acute respiratory diseases; for lactase deficiency, lactose intolerance, lactose/isomaltose malabsorption syndrome, since the drug contains lactose.

Application of Neuromidin 20 mg 50 pcs. pills during pregnancy and breastfeeding

increases uterine tone and can cause premature birth, so it is not recommended to use it during pregnancy. The drug can be used for weak labor. Contraindicated during breastfeeding.

special instructions

There are no systematic data on the use of Neuromidin® in children.

Alcohol should be avoided during treatment. Alcohol increases the side effects of the drug.

Impact on the ability to drive vehicles and operate machinery

During treatment, you should refrain from driving a car, as well as engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms: decreased appetite, bronchospasm, lacrimation, increased sweating, constriction of the pupils, nystagmus, increased peristalsis of the gastrointestinal tract, spontaneous bowel movements and urination, vomiting, jaundice, bradycardia, intracardiac conduction disorders, arrhythmias, decreased blood pressure, restlessness, anxiety, agitation , fear, ataxia, convulsions, coma, speech impairment, drowsiness and general weakness.

Treatment: symptomatic therapy is used, m-anticholinergics are used: atropine, cyclodol, metacin, etc.

Side effects Neuromidin 20 mg 50 pcs. pills

Caused by stimulation of m-cholinergic receptors: salivation, increased sweating, palpitations, nausea; diarrhea, jaundice, bradycardia, epigastric pain, increased secretion of bronchial secretions, bronchospasm, convulsions. Salivation and bradycardia can be reduced with m-anticholinergic drugs (atropine, etc.).

Increased uterine tone, allergic skin reactions.

Rarely, after using higher doses, dizziness, headache, chest pain, vomiting, general weakness, drowsiness, and skin reactions (itching, rash) were observed. In these cases, reduce the dose or interrupt the drug for a short time (for 1-2 days).

These side effects are observed in less than 10% of patients.

Drug interactions

Neuromidin® enhances the sedative effect in combination with drugs that depress the central nervous system.

The action and side effects are enhanced when used together with other cholinesterase inhibitors and m-cholinomimetic drugs.

In patients with myasthenia gravis, the risk of developing a cholinergic crisis increases if Neuromidin® is used simultaneously with other cholinergic drugs.

The risk of developing bradycardia increases if β-blockers were used before starting treatment with Neuromidin®.

Neuromidin® can be used in combination with nootropic drugs.

Reduces the inhibitory effect on neuromuscular transmission and the conduction of excitation along peripheral nerves by local anesthetics, aminoglycosides, and potassium chloride.

Interaction

Neuromidin® enhances the sedative effect in combination with CNS depressants.

The action and side effects are enhanced when used together with other cholinesterase inhibitors and m-cholinomimetic drugs. In patients with myasthenia gravis, the risk of developing a cholinergic crisis increases if Neuromidin® is used simultaneously with other cholinergic drugs.

The risk of developing bradycardia increases if β-blockers were used before starting treatment with Neuromidin®.

Neuromidin® can be used in combination with nootropic drugs.

Alcohol increases the side effects of the drug.

Reduces the inhibitory effect on neuromuscular transmission and the conduction of excitation along peripheral nerves by local anesthetics, aminoglycosides, and potassium chloride.

Directions for use and doses

Inside, s/c or i/m. Doses and duration of treatment are determined individually, depending on the severity of the disease.

Pills

Diseases of the peripheral nervous system:

- mono- and polyneuropathy, polyradiculopathy, myasthenia gravis and myasthenic syndrome of various etiologies - 10-20 mg (0.5-1 tablet) 1-3 times a day. The course of treatment is from 1 to 2 months. If necessary, the course of treatment can be repeated several times with a break between courses of 1–2 months;

— to prevent myasthenic crises, in case of severe disorders of neuromuscular conduction, 1–2 ml (15–30 mg) Neuromidin® 1.5% solution for injection is administered parenterally for a short time, then treatment is continued with Neuromidin® tablets, the dose can be increased to 20–40 mg (1–2 tablets) 5 times a day.

Diseases of the central nervous system: bulbar paralysis and paresis, the recovery period of organic lesions of the central nervous system (traumatic, vascular and other origins), accompanied by motor and/or cognitive impairment - 10–20 mg (0.5–1 tablet) 2–3 times a day day. The course of treatment is from 2 to 6 months. If necessary, the course of treatment is repeated.

Treatment and prevention of intestinal atony - 20 mg (1 tablet) 2-3 times a day for 1-2 weeks.

Solution for intramuscular and subcutaneous administration

Diseases of the peripheral nervous system:

- mono- and polyneuropathy of various origins - subcutaneously or intramuscularly 5-15 mg 1-2 times a day, course - 10-15 days (in severe cases - up to 30 days); then treatment is continued with the tablet form of the drug;

- myasthenia gravis and myasthenic syndrome - subcutaneous or intramuscular 15-30 mg 1-3 times a day with further transition to the tablet form. The general course of treatment is 1–2 months. If necessary, treatment can be repeated several times with a break between courses of 1–2 months.

Diseases of the central nervous system:

— bulbar paralysis and paresis — subcutaneous or intramuscular 5–15 mg 1–2 times a day for 10–15 days; if possible, switch to tablet form;

- rehabilitation for organic lesions of the central nervous system - 10-15 mg intramuscularly 1-2 times a day, course - up to 15 days, then, if possible, switch to tablet form.

If the next dose was not taken on time, then it is not taken additionally.

The maximum daily dose is 200 mg.

Use of the drug Neuromidin

Oral administration For neuritis - 1 tablet 2-3 times a day. The course of treatment is from 10–15 days for acute neuritis, up to 20–30 days for chronic neuritis. If necessary, the course of treatment is repeated 2-3 times with an interval of 2-4 weeks until a therapeutic effect is achieved. For myelopolyradiculoneuritis with paresis of all extremities and prolonged pain - 1 tablet 2-3 times a day for 30-40 days. The course of treatment is repeated many times with a break of 1–2 months until a therapeutic effect is achieved. For myasthenia and myasthenic syndromes, use 1-2 tablets 2-3 times a day. In severe forms, the dose can be increased to 200 mg/day (2 tablets 5 times a day every 2–3 hours). Treatment is a course of treatment, alternating with the use of traditional anticholinesterase drugs. For multiple sclerosis, amyotrophic lateral sclerosis, syringomyelia and other motor neuron diseases (progressive muscle weakness, progressive bulbar palsy) - 1 tablet 3-5 times a day for 60 days 2-3 times a year. For Alzheimer's disease and other forms of mental impairment, start with 1/2 tablet 2 times a day with a gradual increase in dose by 2 tablets per week to 6-10 tablets per day (2 tablets 3-5 times a day). The duration of treatment is from 4 months to 1 year. A course of 4–5 months with a break of 1–2 months is possible. For children with mental retardation, Neuromidin is prescribed at the age of 1–2 years—5 mg (1/4 t of a tablet) once a day, 2–5 years—5 mg (1/4 t of a tablet) 2 times a day, 5-12 years old - 10 mg (1/2 t tablet) 2-3 times a day, over 12 years old - 20 mg (1 tablet) 2-3 times a day. The course of treatment is 1–2 months (depending on the clinical situation). For traumatic brain injuries - 1 tablet 2-3 times a day, if necessary, increase the dose to 120-160 mg/day. Course duration is 30–40 days, 4 courses per year with an interval of 2 months. For primary and secondary weakness of labor - 1-2 tablets per dose, repeated after 1 hour. For intestinal atony - 1/2-1 tablet 3 times a day. Course—1–3 weeks. Parenteral administration In the form of 0.5 and 1.5% solution for injection, administered subcutaneously or intramuscularly. The dose and duration of treatment are determined individually depending on the degree and severity of the disease. For diseases of the peripheral nervous system, myasthenia gravis, 1 ml of 0.5 or 1.5% (5–15 mg) solution is administered subcutaneously or intramuscularly 1–2 times a day. The course of treatment is 1–2 months. If necessary, the course of treatment can be repeated several times with a break between courses of 1–2 months. To relieve myasthenic crisis and conduct short-term courses of treatment in patients with severe disorders of neuromuscular transmission, a 1.5% solution for injection is administered, after which Neuromidin is prescribed orally at a dose of 20 mg. A single dose can be increased to 200 mg/day (1-2 tablets 5-6 times a day). Treatment is a course of treatment, alternating with the use of classical anticholinesterase drugs. For acute mononeuritis, 1 ml of 0.5% solution is prescribed 1–2 times a day in combination with anti-inflammatory and decongestant drugs. The course of treatment is 10–15 days. For chronic neuritis, in case of insufficient therapeutic effectiveness of previous therapy, Neuromidin is prescribed 2 ml of 0.5% solution 1-2 times a day. The course of treatment is 20–30 days. If necessary, the course of treatment is repeated 2-3 times with an interval of 2-4 weeks until the maximum effect is achieved. For myelopolyradiculoneuritis with paresis of all extremities and prolonged pain, 15–20 mg is prescribed 2–3 times a day for 30–40 days, the course of treatment is repeated many times with an interval of 1–2 months. For multiple sclerosis, amyotrophic lateral sclerosis, syringomyelia and other diseases of this group, 20 mg is prescribed 3-5 times a day for 60 days, 2-3 times a year. For Alzheimer's disease and other forms of dementia, treatment begins with a dose of 10 mg 2 times a day with a gradual increase in the dose by 40 mg over the course of a week to 120–200 mg/day. The duration of treatment is from 4 months to 1 year. A course of therapy is possible for 4–5 months with a break of 1–2 months. For children with mental retardation, Neuromidin is prescribed in doses ranging from 5–10 mg 3 times a day to 60–100 mg/day. For traumatic brain injury in the acute period, 3–5 days from the moment of injury, 1–2 ml of 0.5% solution is prescribed 1–2 times a day; after 5–6 days, the dose can be increased to 30–45 mg ( 1.5% solution) 1–3 times a day. In some cases, with severe disorders, intravenous administration of 5% glucose solution or 0.9% sodium chloride solution is possible. The duration of the course is set individually and varies between 30–40 days. In the long-term period of injury, to restore memory, movements, attention, speech, reduce movement disorders, and increase general ability to work, 20 mg 2-3 times a day is prescribed; if the effect is insufficient, the dose is increased to 120-160 mg/day. The duration of the course of treatment is 30–40 days, 4 courses per year with an interval of 2 months. In the acute stage of cerebrovascular accident, 1-2 ml of 0.5% solution is prescribed 2-3 times a day in combination with other drugs, in a prolonged coma, in the presence of bulbar disorders for rapid regression of aphasic, apraxic and amnestic manifestations. In the subacute period, a course of injections of 1–2 ml of 0.5% solution is administered 2 times a day for 30–40 days. In the long-term period - 60-120 mg for 40-60 days, repeated after 1-2 months. To stimulate labor, 20 mg is prescribed 1–3 times with an interval of 1 hour. For primary and secondary weakness of labor, 2 ml of 0.5% solution is prescribed 1–3 times with an interval of 1 hour. For the treatment and prevention of intestinal atony Prescribe 10–20 mg 2–3 times a day for 1–3 weeks.

Overdose

Symptoms: decreased appetite, bronchospasm, lacrimation, increased sweating, constriction of the pupils, nystagmus, increased gastrointestinal peristalsis, spontaneous bowel movements and urination, vomiting, jaundice, bradycardia, intracardiac conduction disturbances, arrhythmias, decreased blood pressure, restlessness, anxiety, agitation, feelings of fear, ataxia, convulsions, coma, speech impairment, drowsiness, general weakness.

Treatment: symptomatic therapy is used, m-anticholinergic blockers are prescribed (atropine, cyclodol, metacin, etc.).

Overdose of the drug Neuromidin, symptoms and treatment

In case of severe overdose, a cholinergic crisis may develop with the following symptoms: bronchospasm, lacrimation, increased sweating, miosis, nystagmus, spontaneous defecation and urination, vomiting, bradycardia, heart block, arrhythmia, arterial hypotension, restlessness, anxiety, agitation, a feeling of fear, ataxia, convulsions, coma, slurred speech, drowsiness and weakness. Symptoms may be mild. In case of Neuromidin poisoning or its relative overdose, M-anticholinergic blockers (atropine sulfate, metacin, cyclodol, etc.) are used.

special instructions

There are no systematic data on the use of Neuromidin® in children.

Alcohol should be avoided during treatment (it increases the side effects of the drug).

Impact on the ability to drive a car or perform work that requires increased speed of physical and mental reactions. During treatment, you should refrain from driving a car, as well as engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Release form

Tablets, 20 mg. 10 tablets each in blister packs made of PVC film and aluminum foil. 5 blister packs per cardboard pack.

Solution for intramuscular and subcutaneous administration, 5 mg/ml and 15 mg/ml. 1 ml of the drug in neutral glass ampoules (type I). 5 amp. in blister packs made of PVC film. 2 blister packs in a cardboard pack.

For the drug produced at SOPHARMA JSC, Bulgaria: 10 amp. in blister packs made of PVC film. 1 blister pack in a cardboard pack.