Noopept: instructions for use (tablets)

Pharmacodynamics

Noopept® has nootropic and neuroprotective properties. Improves learning ability and memory, acting on all phases of processing: initial information processing, consolidation, retrieval. Prevents the development of amnesia caused by electric shock, blockade of central cholinergic structures, glutamatergic receptor systems, and deprivation of the paradoxical phase of sleep.

The neuroprotective (protective) effect of the drug Noopept® is manifested in increasing the resistance of brain tissue to damaging influences (trauma, hypoxia, electroconvulsive, toxic) and reducing the degree of damage to brain neurons. The drug reduces the volume of the lesion in a thrombotic stroke model and prevents the death of neurons in cultured tissue of the cerebral cortex and cerebellum exposed to neurotoxic concentrations of glutamate and free radical oxygen.

Noopept® has an antioxidant effect, blocks voltage-gated calcium channels in neurons, weakening the neurotoxic effect of excess calcium, improves the rheological properties of blood, having antiaggregation, fibrinolytic, and anticoagulant properties.

The nootropic effect of the drug is associated with the formation of cycloprolylglycine, which is similar in structure to the endogenous cyclic dipeptide, which has antiamnestic activity, as well as the presence of a choline-positive effect.

Noopept® increases the amplitude of the transcallosal response, facilitating associative connections between the cerebral hemispheres at the level of cortical structures. Helps restore memory and other cognitive functions impaired as a result of damaging influences - brain injury, local and global ischemia, prenatal damage (alcohol, hypoxia).

The therapeutic effect of the drug in patients with organic disorders of the central nervous system manifests itself starting from 5–7 days of treatment. Initially, the anxiolytic and mild stimulating effects present in the spectrum of activity of the drug Noopept® are realized, manifested in the reduction or disappearance of anxiety, increased irritability, affective lability, and sleep disturbances. After 14–20 days of therapy, a positive effect of the drug on cognitive functions, parameters of attention and memory is revealed.

Noopept® has a vegetative-normalizing effect, helps reduce headaches, orthostatic disorders, and tachycardia.

When discontinuing the drug, no withdrawal syndrome is observed. Does not have a damaging effect on internal organs; does not lead to changes in the cellular composition of the blood and biochemical parameters of blood and urine; does not have immunotoxic, teratogenic effects, does not exhibit mutagenic properties.

Instructions for use

Composition per tablet

Active ingredient: Omberacetam (noopept) - 10.0 mg; excipients: lactose monohydrate - 55.0 mg, potato starch - 13.5 mg, microcrystalline cellulose 101 - 21.2 mg, magnesium stearate - 0.3 mg, povidone (polyvinyl-pyrrolidone, povidone K-25) - 0.0008 mg.

Description

Tablets are white, round, flat-cylindrical with a bevel.

Pharmacotherapeutic group: nootropic agent.

ATX code: N06ВХ

Pharmacological properties

Pharmacodynamics

Noopept® has nootropic and neuroprotective properties. Improves learning ability and memory, acting on all phases of processing: initial information processing, consolidation, retrieval. Prevents the development of amnesia caused by electric shock, blockade of central cholinergic structures, glutamatergic receptor systems, and deprivation of the paradoxical phase of sleep. The neuroprotective (protective) effect of Noopept® is manifested in increasing the resistance of brain tissue to damaging influences (trauma, hypoxia, electroconvulsive, toxic) and reducing the degree of damage to brain neurons. The drug reduces the volume of the lesion in a thrombotic stroke model and prevents the death of neurons in cultured tissue of the cerebral cortex and cerebellum exposed to neurotoxic concentrations of glutamate and free radical oxygen. Noopept® has an antioxidant effect, blocks voltage-dependent calcium channels of neurons, weakening the neurotoxic effect of excess calcium, improves the rheological properties of the blood, having antiplatelet, fibrinolytic, and anticoagulant properties.

The nootropic effect of the drug is associated with the formation of cycloprolylglycine, which is similar in structure to the endogenous cyclic dipeptide, which has antiamnestic activity, as well as the presence of a choline-positive effect.

Noopept® increases the amplitude of the transcallosal response, facilitating associative connections between the cerebral hemispheres at the level of cortical structures. Promotes the restoration of memory and other cognitive functions impaired as a result of damaging influences - brain injury, local and global ischemia, prenatal damage (alcohol, hypoxia).

The therapeutic effect of the drug in patients with organic disorders of the central nervous system is manifested starting from the 5-7th day of treatment. Initially, the anxiolytic and mild stimulating effects present in the spectrum of activity of Noopept® are realized, manifested in the reduction or disappearance of anxiety, increased irritability, affective lability, and sleep disturbances. After 14-20 days of therapy, a positive effect of the drug on cognitive functions, parameters of attention and memory is revealed.

Noopept® has a vegetative-normalizing effect, helps reduce headaches, orthostatic disorders, and tachycardia.

When discontinuing the drug, no withdrawal syndrome is observed.

Does not have a damaging effect on internal organs; does not lead to changes in the cellular composition of the blood and biochemical parameters of blood and urine; does not have immunotoxic, teratogenic effects, does not exhibit mutagenic properties.

Pharmacokinetics

Omberacetam, being absorbed in the gastrointestinal tract, enters the systemic circulation unchanged, penetrates the blood-brain barrier, and is detected in the brain in higher concentrations than in the blood. The time to reach maximum concentration is on average 15 minutes. The half-life from blood plasma is 0.38 hours. Partially remains unchanged, partially metabolized to form phenylacetic acid, phenylacetylproline and cycloprolylglycine. It has high relative bioavailability (99.7%), does not accumulate in the body, and does not cause drug dependence.

Indications for use

Impaired memory, attention, other cognitive functions and emotionally labile disorders (including in elderly patients) with:

• consequences of traumatic brain injury,
• post-concussion syndrome,
• cerebrovascular insufficiency (encephalopathies of various origins),
• asthenic disorders,
• other conditions with signs of decreased intellectual productivity.

Contraindications

Pregnancy, breastfeeding period. Age up to 18 years. Hypersensitivity to the components of the drug. Lactase deficiency, lactose intolerance, glucose-galactose malabsorption. Severe dysfunction of the liver and kidneys.

Use during pregnancy and breastfeeding

The drug is contraindicated for use during pregnancy.

If it is necessary to use the drug during breastfeeding, it is necessary to decide on stopping breastfeeding.

Directions for use and doses

Noopept® is used orally, after meals. Treatment begins with a dose of 20 mg, divided into two doses of 10 mg throughout the day (morning and afternoon). If the therapy is insufficiently effective and the drug is well tolerated, the dose is increased to 30 mg (see “Special Instructions”), distributed into three doses of 10 mg each day. You should not take the drug later than 18 hours. The duration of the course of treatment is 1.5 – 3 months. A second course of treatment, if necessary, can be carried out after 1 month.

Side effect

Allergic reactions are possible. In patients with arterial hypertension, mostly severe, while taking the drug, a rise in blood pressure may be observed.

Overdose

Specific manifestations of overdose have not been established.

Interaction with other drugs

The interaction of Noopept® with alcohol, hypnotic and antihypertensive drugs and psychostimulant drugs has not been established.

special instructions

If it is necessary to increase the dose of the drug (up to 30 mg/day), with long-term use, as well as with simultaneous use with other drugs, the occurrence of adverse reactions or worsening of the condition, you should consult a doctor.

Impact on the ability to drive vehicles and machinery

Noopept® does not affect the ability to operate machinery and vehicles.

Release form

Tablets, 10 mg.

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

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

Storage conditions

At a temperature not higher than 25°C.

Keep out of the reach of children.

Best before date

3 years.

Do not use after the expiration date stated on the package.

Vacation conditions

Available without a prescription.

Marketing authorization holder/organization receiving consumer complaints

OTCPharm JSC, Russia 123112, Moscow, st. Testovskaya, 10, fl. 12, room II, room 29 Tel. Fax

, Russia, 305022, Kursk, st. 2nd Aggregatnaya, 1a/18, tel./fax

Pharmacokinetics

N-phenylacetyl-L-prolylglycine ethyl ester, absorbed in the gastrointestinal tract, enters the systemic circulation unchanged, penetrates the BBB, and is determined in the brain in higher concentrations than in the blood. Tmax averages 15 minutes. T1/2 from blood plasma - 0.38 hours. Partially stored unchanged, partially metabolized with the formation of phenylacetic acid, phenylacetylproline and cycloprolylglycine. It has high relative bioavailability (99.7%), does not accumulate in the body, and does not cause drug dependence.

Indications

Noopept is indicated for a fairly large number of conditions:

• impairments of cognitive functions of various origins;
• emotional-volitional disorders (including in the elderly);
• consequences of traumatic brain injury (brain contusion, diffuse axonal damage);
• post-concussion syndrome;
• discirculatory encephalopathy, encephalopathy of combined genesis (with the presence of a vascular component);
• asthenia;
• decrease in intellectual activity of various origins.

The term “moderate cognitive impairment” (MCI) is used to describe mono- or multifunctional cognitive disorders that go beyond the age norm, but do not limit autonomy and independence, i.e. do not cause maladjustment in everyday life. The prevalence of MCI among the elderly, according to population studies, reaches 12-17% [2, 8, 9]. Among neurological patients, MCI syndrome occurs in 44% of cases [5, 6, 11]. MCI often becomes progressive, eventually transforming into vascular or mixed (neurodegenerative) dementia.

In the structure of vascular cognitive disorders, it was proposed to consider vascular dementia itself, impairment of cognitive functions due to a combination of vascular and neurodegenerative pathology of the brain (mixed dementia) and vascular cognitive disorders that do not reach the level of dementia [12, 14].

Stroke is one of the causes of cognitive impairment. Morphological changes in the brain leading to the development of cognitive disorders in stroke patients can be [8]: a single stroke in a region of the brain that is strategically important for cognitive functions (frontal cortex, parieto-occipital junction, thalamus, corpus callosum, some parts of the cerebellum and etc.); recurrent strokes; multiple “silent” lacunar strokes; significant damage to the white matter (leukoaraiosis).

Cognitive impairment also occurs due to cerebral hypoperfusion as a complication during operations on the vessels of the head and neck, during operations using artificial circulation. They are often mild in nature and may not be noticed by either surgeons or the patients themselves. Some MCI does not develop immediately after a cerebrovascular event, but rather in a delayed manner, several weeks or months later. This is due to progressive neurodegeneration after a triggering factor in the form of a stroke.

Results from randomized controlled trials of the effectiveness of various drugs in MCI are limited and variable. In this regard, there are no clear therapeutic recommendations and only general strategies for preventing the development of MCI, aimed at eliminating cardiovascular risk factors and neuroprotection, are proposed. Implementation of these strategies involves the use of both pharmacological and non-pharmacological treatments.

Nootropics and neuroprotectors are used in the treatment of MCI. Noopept is one of the modern drugs with claimed nootropic and neuroprotective properties. It is the ethyl ester of N-phenyl-acetyl-L-prolyl-glycine, and its active metabolite, cycloprolylglycine, is identical to the endogenous cyclic dipeptide with nootropic and neuroprotective activities [1, 3]. Previous studies have shown that noopept facilitates not only the processes of initial information processing, its fixation and consolidation, but also its retrieval. This distinguishes it from other nootropics, which primarily affect the initial phases of information processing [1, 3]. The drug has been studied in adults with memory impairment, attention, and other cognitive disorders arising after traumatic brain injury and chronic cerebrovascular insufficiency. In therapeutic doses, noopept is well tolerated and does not cause anxiety or insomnia [3]. The effectiveness of noopept has been shown in the treatment of MCI in patients with discirculatory encephalopathy stages I and II, not only in the form of a decrease in cognitive impairment according to neuropsychological tests, but also an improvement in the results of a study of cognitive evoked potentials - P300 [3].

Taking into account the pathogenetic differences between acute and chronic cerebrovascular accidents, the purpose of this study was to evaluate the effectiveness and tolerability of noopept in the treatment of MCI in patients with ischemic stroke.

Material and methods

The open-label prospective study included 60 patients, 30 men and 30 women, aged from 50 to 80 years. During the last year before inclusion in the study, they suffered an ischemic stroke verified by neuroimaging (CT or MRI of the brain).

Syndromic diagnosis of MCI was carried out in accordance with the criteria developed by R. Petersen, J. Touchon [cit. according to 7, 10, 13].

The patients' medical history was collected and physical and neurological examinations were performed. To assess cognitive function before and after treatment, neuropsychological testing was performed using the Mini Mental State Examination (MMSE); clock drawing test; test of literal and categorical associations [4]. When the patient was included in the study, a score was given on the Hospital Anxiety and Depression Scale [15]. Overall assessment of clinical effectiveness was carried out at the beginning and end of treatment using the Global Clinical Impression of Change (GCIC) scale [9] and a formal scale for assessing subjective neurological symptoms.

The main group consisted of 30 patients, 16 men and 14 women (average age - 62.03±1.40 years), with a stroke duration of 6.14±0.30 months. Patients in the main group were prescribed Noopept at a dose of 10 mg 2 times a day after meals for 2 months. The comparison group included 30 patients, 14 men and 16 women (average age - 62.83±1.54 years), with a stroke duration of 6.83±0.38 months, with similar clinical and demographic parameters, who did not receive treatment with noopept . Patients in both groups continued treatment with antihypertensive, antiplatelet, and hypocholesterolemic drugs as indicated.

Patients excluded from the study were: under 50 or over 80 years of age; unable for any reason to take the drug orally; with concomitant severe or decompensated somatic diseases; the presence of cognitive disorders at the level of dementia or other mental disorders; the presence of gross motor, speech or sensory defects that impede the conduct of studies provided for in the test protocol; concomitantly using other vasoactive, neurometabolic or psychotropic drugs; with individual intolerance to noopept.

The safety and tolerability of treatment were assessed in accordance with the frequency and severity of adverse events that were recorded while taking the drug, as well as the dynamics of vital functions (blood pressure, heart rate).

Statistical processing of the obtained data was carried out using the parametric Student's t-test and the non-parametric Mann-Whitney test.

Results and discussion

The main causes of ischemic stroke in the examined patients were hypertension - in 58 (96.6%), atherosclerosis of the brachiocephalic arteries - in 29 (48.3%), atherosclerosis of the intracranial arteries - in 9 (15%), cardiogenic embolism - in 17 (28.3%), diabetic angiopathy - in 2 (3.33%). 8 (13.3%) patients had a history of transient ischemic attacks. According to the location of the ischemic focus in the main group, left hemisphere stroke was detected in 14 (46.6%) patients, right hemisphere - in 12 (40%), stroke in the vertebrobasilar region (VBB) - in 4 (13.3%). In the comparison group, left hemisphere stroke was detected in 12 (40%) patients, right hemisphere stroke - in 13 (43.3%); stroke in the VBB - in 5 (16.6%). By the start of the study, the value of the Rankin self-care ability scale in the main group was 0.93±0.13 points, in the control group - 0.83±0.13 points, i.e. identical.

All 60 patients of the main and control groups completed the study. After 2 months of observation, analysis of MMSE indicators revealed a significant improvement in cognitive function indicators in patients of both groups, while in the group treated with noopept, these indicators improved significantly more significantly (Table 1).

When analyzing the results of the clock drawing test, no significant differences were found between the groups, although patients in the main group showed a tendency to improve the performance of this test, which may indicate some positive effect of noopept on concentration.

Evaluation of indicators of literal and categorical associations revealed a significant improvement in the performance of the categorical association test by patients receiving noopept (Table 2).

The overall assessment of the effectiveness of therapy, according to the GCIC scale, in the group of patients receiving noopept corresponded to a moderate improvement; in the control group, no changes were detected on this scale.

After 2 months of observation, the values ​​on the Rankin scale (level of self-care) in the main and control groups did not change.

During the study, no significant adverse reactions were identified when taking Noopept. Not a single patient refused to take the drug.

Thus, the results of an open study indicate that noopept in a daily dose of 20 mg, used for 2 months, improves cognitive function in patients who have suffered an ischemic stroke and has a high level of safety. The results of domestic studies of the effectiveness and safety of noopept obtained to date allow its use in the complex treatment of vascular MCI.

Noopept

Trade name: Noopept

International name: (not specified) ( (not specified))

Release form: tablets 10 mg (polymer jars, blister packs)

Ingredients: phenylacetylprolylglycine ethyl ester [noopept] 10 mg

Pharmacological group: nootropic agent

Pharmacological group according to ATK: N06BX (Psychostimulants and other nootropics)

Pharmacological action: nootropic, antihypoxic,

Ingredients: phenylacetylprolylglycine ethyl ester (noopept) 10 mg

Indications: Impaired memory, attention, ability to perceive and assess reality, incl. in the elderly, consequences of head injury, chronic cerebral circulatory insufficiency (including after a stroke) with signs of decreased intelligence, emotionally labile disorders.

Dosage regimen: Inside, after meals. The initial dose is 20 mg, divided into 2 doses during the day (morning and afternoon). If there is insufficient effectiveness and good tolerability, the dose is increased to 30 mg, divided into 3 doses during the day. You should not take the drug later than 18 hours. The course of treatment is 1.5-3 months. If necessary, it is possible to conduct a second course after 1 month.

Contraindications: Hypersensitivity, severe renal/liver failure, pregnancy, lactation, age under 18 years.

Side effects: Allergic reactions, increased blood pressure in patients with arterial hypertension.

Pharmacodynamics: Has nootropic and neuroprotective effects. Improves learning ability, memory, acting on all phases: initial information processing, consolidation, retrieval. Prevents the development of amnesia caused by electric shock, blockade of central cholinergic structures, glutamatergic receptor systems, and deprivation of the paradoxical phase of sleep. The neuroprotective effect is manifested in increasing the resistance of brain tissue to damaging influences (trauma, hypoxia, electroconvulsive, toxic) and reducing the degree of damage to brain neurons. The drug reduces the volume of the lesion in a thrombotic stroke model and prevents the death of neurons in cultured tissue of the cerebral cortex and cerebellum exposed to neurotoxic concentrations of glutamate and free radical oxygen. It also has an antioxidant effect, an antagonistic effect on the effects of excess Ca2+, improves the rheological properties of blood, having antiplatelet, fibrinolytic, anticoagulant properties. The nootropic effect of the drug is associated with the formation of cycloprolylglycine, which is similar in structure to the endogenous cyclic dipeptide, which has antiamnestic activity, as well as the presence of cholinergic stimulating effects. Increases the amplitude of the transcallosal response, facilitating associative connections between the cerebral hemispheres at the level of cortical structures. Promotes the restoration of memory and other cognitive functions impaired as a result of damaging influences (brain trauma, local and global ischemia, prenatal damage caused by ethanol, hypoxia). The therapeutic effect of the drug in patients with organic lesions of the central nervous system manifests itself from 5-7 days of treatment. Initially, anxiolytic and mild stimulating effects are realized, manifested in a decrease or disappearance of anxiety, increased irritability, affective lability, and sleep disturbances. After 14-20 days of therapy, a positive effect of the drug on cognitive functions, parameters of attention and memory is revealed. It has a vegetative-normalizing effect, helps reduce headaches, orthostatic disorders, and tachycardia.

Pharmacokinetics: Relative bioavailability - 99.7%. Absorbed in the gastrointestinal tract, it enters the systemic circulation unchanged, penetrates the BBB, and is determined in the brain in higher concentrations than in the blood. TCmax - 15 min. T1/2 from plasma - 0.38 hours. Partially metabolized with the formation of phenylacetic acid, phenylacetylproline and cycloprolylglycine.

Dispensed from pharmacies: Dispensed without a prescription.

Drug registration number: LS-001577

Date of registration (re-registration) of the drug: 05/12/2006