RU2300389C1 - Nootropic agent - Google Patents

Abstract

FIELD: medicine, phytotherapy, pharmacy.

SUBSTANCE: invention relates to development of medicinal preparations based on vegetable materials with displaying the nootropic effect. Invention proposes using birch bark as a nootropic agent. Agent provides mild effect and without adverse effect.

EFFECT: valuable medicinal properties of agent.

10 dwg

Description

The invention relates to medicine, more specifically to psychopharmacology, and even more specifically to finding new nootropic drugs.

Nootropics (Greek noos - thinking, reason; tropos - direction) - means that have a specific positive effect on the higher integrative functions of the brain. They improve mental activity, stimulate cognitive functions, learning and memory, increase brain resistance to various damaging factors, including to extreme loads and hypoxia. In addition, nootropics (neurometabolic stimulants) have the ability to reduce neurological deficits.

The concept of nootropic drugs arose in 1963 when the Belgian pharmacologists S. Giurgea and V. Skondia synthesized and introduced the first drug of this group - piracetam. Subsequent studies have shown that piracetam facilitates learning processes and improves memory. Like psychostimulants, the drug increased mental performance, but at the same time did not have the side effects inherent in psychostimulants.

After the successful introduction of piracetam into medical practice, more than 10 original nootropic drugs of the pyrrolidine series were synthesized, which are currently in phase III clinical trials or already registered in several countries: oxiracetam, aniracetam, etiracetam, pramiracetam, dupracetam, rolziracetam, cebracetam, nefiracetam, isacetam , detiracetam, etc. These nootropic drugs, on the basis of their chemical structure, are called "racetams." Following them, other families of nootropic drugs began to form, including cholinergic, GABAergic, glutamatergic, peptidergic and other substances; in addition, nootropic activity was identified in some previously known substances.

A number of substances belonging to the group of nootropic drugs has a fairly wide spectrum of pharmacological activity, including antihypoxic, anxiolytic, sedative, anticonvulsant, muscle relaxant and other effects.

The stimulating effect of nootropics on mental activity is not accompanied by speech and motor excitement, depletion of the body's functional capabilities, development of addiction and addiction, although in some cases they can cause anxiety and sleep disturbance. A positive property of nootropics is their low toxicity, good compatibility with drugs of other pharmacological groups and the practical absence of side effects and complications.

Recently, a high pace of research activities associated with the search and study of the mechanism of action of new and existing nootropic drugs has been noted. The search for new drugs that would have greater pharmacological activity and have a selective effect on the integrative functions of the brain, improving the patient's psychopathological state, his mental activity and orientation in everyday life, is relevant.

One of the directions in the search for new nootropics is the study of plant products for the presence of nootropic activity.

Known herbal nootropic drug sold under the brand name "Tanakan" (Tanakan), which is a standardized extract from the leaves of Ginkgo biloba. However, Ginkgo biloba is a relict tree with an extremely narrow distribution area; therefore, the task of finding new effective and inexpensive herbal preparations with nootropic activity continues to be relevant.

The authors of the present invention as a result of a series of studies, nootropic activity was found in the birch bark extract - the upper, white part of the birch bark - one of the most common tree species in the world. The use of such an extract as a nootropic agent determines the essence of the present invention.

Psychotropic activity was identified by the inventors in studies of “Birch bark of dry extract” (hereinafter abbreviated as BES), produced by Birch World Limited Liability Company (Moscow, Russia) for the manufacture of food additives. The main component of birch bark extract is betulin.

Initially, the pharmacokinetics of BES was studied, and it was found that when it was administered once to rats at a dose of 100 mg / kg, the maximum concentration in the brain tissue (114 ± 6 μg / g) was observed 2 hours after administration, while the maximum concentration BES in the blood (189 ± 11 μg / ml) is achieved only after 3 hours.

Further experiments were carried out on male mice of the C57 / BI / 6 line with a mass of 20-25 g contained in a laboratory vivarium on a standard diet.

BES was administered to mice using a probe intragastrically in the form of a suspension in a 1% solution of potato starch at doses of 25, 50 and 100 mg / kg 1.5 hours before testing. The control group was administered equivalent volumes of 1% starch. In experiments with acute administration of the drug, the control and 3 experimental groups of animals consisted of 16-20 individuals each. In experiments with repeated administration of BAS, 1 control and 1 experimental group of animals were used (50 mg / kg / day).

When processing the obtained results, we used the methods of parametric and nonparametric statistics (student t-test, Chi-square, etc.) according to the “Methodological recommendations for experimental (preclinical) study of new pharmacological substances”, Moscow, 2000.

For a preliminary assessment of the possible psychotropic effect of BES, a complex of two tests was used - the so-called “Cross-shaped labyrinth” and “slippery funnel”, which allows registering the nature of their behavior in an unfamiliar and unavoidable situation in two consecutive passages of animals and calculating behavior parameters that reflect anxiety, motor activity, reaction to novelty, and rationality of movement in a new environment.

Cruciform Maze Test

The cross-shaped labyrinth consists of 4 transparent plastic closed empty compartments, which were numbered 1-4 and connected to the same central compartment using inlets [see Salimov R.M., Sinclair J.D. Behavioral predictors of alcohol use in rats and mice // Biological basis of individual sensitivity to psychotropic drugs / Eds. Seredenin S.B., Longo V., Gaviraghi G. Edinburgh: Graffham Press Ltd., 1994. - P.203-211]. The labyrinth floor was cleaned before each experiment. The animal was placed in the central compartment and allowed him to examine the maze. In fact, the labyrinth was a structured analogue of the open field test, but unlike the latter, it allowed a quantitative measurement of the animal’s research behavior regardless of the magnitude of its motor activity. Using a personal computer, the sequence of movements of the animal and the duration of its stay in different parts of the maze were recorded. The criterion for entering the labyrinth compartment was the presence of all four animal paws inside this room. The experiment continued until the animal made 12 transitions from one side compartment to another (that is, until it made 13 visits to the side compartments). Subsequent analysis of the data allowed us to identify the following indicators.

1. The latent period of the beginning of research behavior (FLAT), that is, the time elapsed before the first entry into the side compartment, and the length of stay in the first impasse. These parameters have a negative correlation with the length of stay in the open arms of the raised maze and can be considered as an indicator of the balance between the curiosity and anxiety of the animal in the new environment.

2. The number of visits to the side compartments during the first and second patrols of the maze (that is, visits to all its premises) (FPAT). For example, if the sequence of numbers of the side compartments visited was 1241413344321, then 7 visits were spent on the first patrol. The more visits are required to completely bypass the maze, the less effective is the research behavior of this individual.

3. The total number of patrols (PATN). In the above example, this figure is 2, since the second patrol was completed at the 13th visit. The more patrols of the maze were observed, the more effective is the research behavior of this animal.

4. The total length of stay in the center and arms of the labyrinth, which has an inverse correlation with the number of crossed squares in the open field test [Markina N.V., Salimov R.M., Poletaeva I.I. Exploratory behavior of F2 crosses of mouse lines having selected for different brain weight: A multivariate analysis. Prog. Neuro-Psychopharmacol. Biol. Psychiat. 2004, 28 (3): 583-589].

Slippery funnel test

A slippery funnel consists of a wide upper cylindrical part, a middle part having the shape of a funnel (the angle between the wall and the horizontal is 40 °), and a narrow lower part. The lower cylindrical segment of the funnel was immersed in a vessel with water (22 ° C), which was changed before each experiment. The depth of the water was such that when the animal stood motionless at the bottom, its hind legs were immersed in water [see Salimov R.M., Sinclair J.D. Behavioral predictors of alcohol use in rats and mice // Biological basis of individual sensitivity to psychotropic drugs / Eds. Seredenin S.B., Longo V., Gaviraghi G. Edinburgh: Graffham Press Ltd., 1994. - P.203-211]. The test began by placing the animal in water in the lower part of the funnel and lasted 3 minutes. During this time, the following categories of behavior were recorded using a personal computer.

1. Duration of stay in water at the bottom of the funnel (FIMM).

2. The duration of passive avoidance of the situation in the form of an attempt to stay in a flattened pose on the inclined funnel wall (FAVO).

3. The duration of the active avoidance of the situation in the form of attempts to get out or jump out of the funnel (FESC).

This test was used as an alternative to the famous Porsolt forced swimming test in order to minimize the influence of such side factors as unequal physical performance and body buoyancy in different individuals. It was previously found that the first and third indicators of the slippery funnel test have respectively positive and negative correlations with the “despair behavior” in the Porsolt forced swimming test [Salimov R.M. Different behavioral patterns related to alcohol use in rodents: A factor analysis // Alcohol. - 1999. - 17. P.157-162].

Using these tests, the following studies were conducted.

1. The study of the behavior profile of mice in tests “cross-shaped labyrinth” and “slippery funnel” after a single injection of BES inside at doses of 25, 50 and 100 mg / kg after 2 hours

2. The study of the behavior profile of mice in tests “cross-shaped labyrinth” and “slippery funnel” after a single injection of BES inside at doses of 25, 50 and 100 mg / kg after 6 hours

3. The study of the behavior profile of mice in the test "cruciform labyrinth" after subchronic administration of BAS inward at a dose of 50 mg / kg / day for 5 days.

1. A study of the behavior of C57BI mice in the tests “cross-shaped labyrinth” and “slippery funnel” 2 hours after a single administration of BES inside the doses of 25, 50 and 100 mg / kg.

a) The influence of BES on the number of visits spent by mice on the 1st and 2nd patrols of the maze (average values and confidence interval).

Analysis of the data using the non-parametric Chi-square test revealed a statistically significant decrease in the number of visits spent on the 2nd patrol. In control, in 8 out of 15 mice, this indicator was more than 5, and after administration of BAS at a dose of 25 mg / kg, only in 2 out of 15 mice (p = 0.02) (Figure 1).

This effect is characteristic of the action of nootropic drugs.

b) The influence of BES on the latent period of the first call (time in the center) and the duration of the first visit (time at a dead end) to the dead end of the labyrinth (average values and confidence interval).

Comparison of student averages did not reveal differences, however, analysis of the data using the non-parametric Chi-square test revealed a statistically significant increase in the latency of the first call. In the control of none of the 15 mice, this indicator did not exceed 19.5 seconds, and after BES at a dose of 25 mg / kg in 4 out of 15 mice it was greater than the indicated value (p = 0.032). A close result was observed after BAS at a dose of 50 mg / kg - in 3 out of 15 mice this indicator was greater than the specified value (p = 0.068) (figure 2).

Selective (compared with the indicators shown in figure 3) an increase in this indicator is characteristic of funds that enhance alertness and vigilance. The shortening of these indicators is typical for the action of tranquilizing agents.

c) The influence of BES on the total length of stay in the center and in the dead ends of the maze without taking into account the indicators shown in figure 2 (average values and confidence interval).

Analysis of the data using the non-parametric Chi-square test revealed a statistically significant decrease in the total length of stay in the center of the maze. In the control of 5 out of 15 mice, this indicator was more than 63 seconds, and after BES at a dose of 25 mg / kg, none of the 15 mice (p = 0.014) (Fig. 3).

The shortening of these indicators is typical for the action of timoleptic and psychostimulating agents, and their lengthening is for sedatives.

d) The effect of BES on the total time of immobility, passive or active avoidance of a slippery funnel in the test (average values and confidence interval).

A comparison of the Student averages showed a statistically significant increase in the total passive avoidance time (t (1.26) = 2.61, p = 0.032) (Fig. 4).

An increase in passive and active avoidance is characteristic of the effects of timoleptic and antidepressant drugs.

2. A study of the behavior of C57BI mice in the tests “cross-shaped labyrinth” and “slippery funnel” 6 hours after a single administration of BES inside the doses of 25, 50 and 100 mg / kg.

a) The influence of BES on the number of visits spent by mice on the 1st and 2nd patrols of the maze (average values and confidence interval).

Comparison of student averages did not reveal differences, however, analysis of the data using the non-parametric Chi-square test found a statistically significant decrease in the number of visits spent on the 1st patrol. In the control of 4 out of 15 mice, this indicator was more than 7, and after BAS at a dose of 50 mg / kg, none of the 15 mice (p = 0.014) (Fig. 5).

This effect is characteristic of the action of nootropic drugs.

3. The study of the behavior of C57BI mice in the test "cruciform labyrinth" after 5-fold administration of BAS inward at a dose of 50 mg / kg.

a) The influence of BES on the latent period of the first call (time in the center) and the duration of the first visit (time at a dead end) to the dead end of the labyrinth (average values and confidence interval).

Analysis of variance revealed a tendency to increase both indicators under the influence of administration of BAS at a dose of 50 mg / kg (F (1.32) = 3.885, p = 0.057) (Fig. 6).

In the conducted behavioral tests of the general preliminary screening in mice, it was found that the birch bark extract shows a mild psychotropic effect, the profile of which can be described as moderately activating, energizing, timoleptic.

Further, the study of the effects of BAS was carried out in the corresponding specific directed screening tests, recommended for the detection of nootropic, antidepressant and psychostimulating activity, using doses of 25 and / or 50 mg / kg. In choosing the exposure time of the drug, we were guided by the results obtained when studying the pharmacokinetics of BES (1.5-2 hours), when the level of the drug in the blood and brain approached the maximum values.

The following tasks were solved.

- To study the effect of BAS in standard neuropharmacological tests based on interaction with substances that activate the central nervous system:

a) by the effect on the effects of an antidepressant with an activating component - pyrazidol in the "despair test";

b) the effect on motor hyperactivity caused by the introduction of phenamine and apomorphine.

- To study the behavior profile of C57BI / 6 mice for the detection of nootropic activity according to the standard method of conditioned passive avoidance reflex (passive avoidance reaction) 1.5 hours after a single BES inward at doses of 25 and 50 mg / kg.

Despair Test

Refers to tests aimed at studying the possible effect of the drug on the emotional stress state of animals. This condition is caused in mice by forced swimming.

Mice are placed in a cylinder with a diameter of 10 cm, a height of 25 cm, filled 2/3 with water (27 ° C). After unsuccessful attempts to get out of the water, animals adopt a characteristic motionless pose, which is regarded as a manifestation of depression, “despair”. All active attempts of mice to get out of water during the first 6 minutes after immersion in water are recorded, in particular:

- the duration of free swimming, (s);

- the duration of swimming at the side (s); as well as

- the duration of immobility (s).

Under the influence of antidepressants, regardless of the mechanism of their action, the activity of animals increases and the time of immobility (immobilization) decreases.

In the present experiment, an antidepressant with an activating component of the action of pyrazidol in a standard dose of 25 mg / kg, which was administered intraperitoneally 30 minutes before testing, was used as a comparison drug.

The experiment involved 4 groups of animals.

1. The control group (1% starch - inside, saline - in / b).

2. Comparison group 1 (1% starch - inside, pyrazidol - in / b).

3. Comparison group 2 (BES - inside, saline - in / b).

4. The experimental group (BES - inside, pyrazidol - in / b).

Test "motor activity"

The possibility of the influence of 50 mg / kg BAS on hyperactivity caused by selected doses of phenamine (1 mg / kg, ip) and apomorphine (1 mg / kg, ip) was assessed by the change in the motor activity of mice in a special actometric unit “Ugo Basile” (Italy), registering the horizontal movements of animals. Strengthening of locomotion is associated with activation under the influence of stimulants of dopaminergic activity in the mesolimbic and extrapyramidal systems of the brain. Registered movements in arbitrary units for 2 five-minute periods separately and in total.

The experiment involved 6 groups of animals (N = 8-10).

1. Group 1 (1% starch - inside, saline - in / b).

2. Group 2 (BES - inside, saline - in / b).

3. Group 3 (1% starch - inside, phenamine - in / b).

4. Group 4 (1% starch - inside, apomorphine - in / b),

5. Group 5 (BES - inside, phenamine - in / b).

6. Group 6 (BES - inside, apomorphine - in / b).

Usually, the effect of phenamine is enhanced by drugs with antidepressant activity. Different antidepressants affect the hyperactivation caused by apomorphine differently, depending on the mechanism of action and doses of the psychostimulant.

The impact on learning in the methodology of the conditioned reflex of passive avoidance (passive avoidance reaction).

The test is a basic model for assessing the effect of substances on the formation and reproduction of a commemorative footprint in the norm and in the conditions of its violation (amnesia). The main advantages of this technique are the speed of reflex development (learning from one sample) and the ability to differentially act on different phases of memory.

The development of a conditioned avoidance reflex was carried out using electrodermal stimulation in a special two-chamber installation with an electric floor “Ugo Basile” (Italy). The selection of irritation parameters was carried out experimentally. A check of the persistence of the avoidance reflex was carried out 24 and 48 hours after training. A “breakdown” of the reflex (amnesia) was caused by the introduction of an experimentally selected dose of scopolamine immediately after an animal training session.

The duration of the latent period of the first entry into the hazardous compartment, the number of entries and the time spent in it were recorded.

The experiment involved 6 groups of animals (N = 8-10).

1. Group 1 (placebo - inside 90 minutes before training, saline - in / b immediately after training).

2. Group 3 (BES, 25 mg / kg - inside 90 minutes before training, saline - immediately after training in / b).

3. Group 4 (BES, 50 mg / kg - inside 90 minutes before training, saline - in / b immediately after training).

4. Group 2 (placebo - inside 90 minutes before training, scopolamine - in / immediately after training).

5. Group 5 (BES (25) - inside 90 minutes before training, scopolamine - in / immediately after training).

6. Group 6 (BES (50) - inside 90 minutes before training, scopolamine - in / immediately after training).

For substances with a nootropic effect, the elimination of scopolamine amnesia is characteristic, which is characterized by an increase in the latent period of entry into the hazardous compartment of the chamber and a decrease in the residence time when reproducing passive avoidance reaction.

The following are the results of the study using these tests.

4.1. A study of the behavior of C57BI mice in the despair test 2 hours after a single administration of BES inside a dose of 25 mg / kg. The experimental data (table 1, Fig. 7) indicate that BAS at a dose of 25 mg / kg (group 3) slightly increases (+ 16%), and the antidepressant pyrazidol (group 2) reduces (-22%) the duration of immobility in the test, however, these results are not statistically significant.

At the same time, the introduction of pyrazidol against the background of BAS leads to a significant decrease (-58% to the control and -46% relative to the effect of pyrazidol) in the immobility time of animals in the test (Table 1, Fig. 7):

Table 1. Groups of mice N Average time (s) Stand. mistake t Df p The control 10 441.9 86.4 PIRazidol 10 344.1 31.9 1.06 eighteen 0.302 BES 10 514.6 58.2 -0.70 eighteen 0.494 BES + PIR 10 185.6 * # 58.2 2.46 eighteen 0.024 Note: * / # is a statistically significant difference from Group 1 / Group 2.

Therefore, this dose of BAS almost doubles the anti-immobilization effect of the antidepressant pyrazidol.

On the contrary, indicators of the duration of swimming at the rim under the influence of pyrazidol increased by 24% relative to the control (group 1), BES itself did not increase the duration of the active response to the stressful situation on this parameter, but it doubled the activating effect of pyrazidol (+ 55% relative to groups 1 and +25 % relative to group 2) (Table 2, Fig. 7) against the background of preliminary administration.

Table 2. Groups of mice N Average time (s) Stand. mistake t Df p The control 10 541.4 62.0 PIRazidol 10 671.1 * 52.6 -1.59 eighteen 0.059 BES 10 503.7 58.3 0.44 eighteen 0.663 BES + PIR 10 836.4 * # 79.8 -2.92 eighteen 0.009 Note: * / # is a statistically significant difference from Group 1 / Group 2.

The presented data indicate the activating effect of BAS on the effect of Pyrazidol, expressed in an increase in the period of stay of animals in active attempts to get out of the water.

Thus, BAS exhibits the properties of a positive modulator of the effect of Pyrazidol in two main parameters of the test for the detection of antidepressant activity.

4.2. Study of the effect of BAS (50 mg / kg), phenamine (1 mg / kg), apomorphine (1 mg / kg) and their combinations on the motor activity of C57BI mice.

This test compared the effects of BAS, phenamine, apomorphine, and their paired combinations on the motor activity of animals. The horizontal activity of mice was recorded over two consecutive 5-minute periods, as well as their sums.

It was found that the main differences in the effects are manifested during the first five-minute period (Table 3), which is reflected in the results of recording the total activity (Table 4).

Table 3 Groups of mice N Average time (sec.) Stand. mistake t Df p The control 10 359.3 25,4 BES 8 433.1 * 28,4 -2.19 16 0,043 Phenamine 10 419.9 # 25,4 -1.80 eighteen 0,089 Apomorphine 10 448.8 * 25,4 -2.15 eighteen 0,045 BES + Hairdryer 9 410.2 # 26.8 -1.77 17 0,095 BES + Apo 9 352.4 26.8 0.20 17 0.845 Note: * is a statistically significant difference from Group 1.
# - a pronounced tendency to differ from Group 1.

The data indicate that the introduction of BAS is reflected in a statistically significant increase in horizontal movements of mice by 21% relative to the control, which corresponds to the stimulating effect of apomorphine (+ 25%). Phenamine also shows a tendency to motor activation (+ 17% at 0.05 <p <0.1). However, against the background of the introduction of BAS, its effect persists (+ 14%), while the effect of apomorphine is not manifested at all.

Table 4. Groups of mice N Average time (s) Stand. mistake t Df P The control 10 617.8 45.8 BES 8 739.0 * 51,2 -2.04 16 0.058 Phenamine 10 700.3 45.8 -1.55 eighteen 0.139 Apomorphine 10 757.5 45.8 -1.66 eighteen 0.114 BES + Hairdryer 9 681.8 48.3 -1.28 17 0.218 BES + Apo 9 601.0 48.3 0.27 17 0.787 Note: * is a statistically significant difference from Group 1.

The number of movements over a ten-minute interval retains the main differences in the effect of the tested drugs, although to a lesser extent.

The presented data demonstrate the ability of BAS to increase the motor activity of mice, which is quantitatively comparable with the effectiveness of the comparison drugs. However, the absence of a cumulative effect may indicate a difference in the mechanisms of their implementation between BES, on the one hand, and phenamine and apomorphine, on the other.

5. The study of the effect of BAS in doses of 25 and 50 mg / kg on learning in the test of conditioned reflex of passive avoidance (passive avoidance reaction).

This standard test was used to clarify the assumptions about the presence of nootropic properties in BES arising from the results of a study of the effect of the drug on the behavior of mice in a cruciform maze.

The data presented in Figs. 8, 9, 10 confirm the previously obtained data on the effect of BES on the conditioned-reflex component of animal behavior.

So Fig. 8 demonstrates that punishment causes an increase in the latent period of entry into the dark chamber both after 24 hours and after 48 hours compared with the 1st visit that occurred before the punishment (F (1.77) = 14.75, p <0.001).

The introduction of the amnesic-causing Scopolamine immediately after punishment causes a shortening of the latent period of entry into the dark chamber 24 hours after the punishment compared to saline (F (1.77) = 4.94, p = 0.029).

The preliminary administration of BAS in doses of 25 and 50 mg / kg in combination with Scopolamine counteracts the effect of Scopolamine (causes an increase in the latent period of entry into the dark chamber 24 hours after punishment) compared with the group receiving Scopolamine against a placebo (F (1.77) = 5.07, p = 0.027).

The data presented in Fig. 9 testify to the same direction of the BES effect: the administration of Scopolamine immediately after punishment causes a shortening of the total time spent in the light chamber 24 and 48 hours after punishment compared to saline (F (1.77) = 43.01 , p <0.001).

The preliminary administration of BES in doses of 25 and 50 mg / kg in combination with Scopolamine also counteracts this effect of Scopolamine, causing an increase in the total time spent in the light chamber 24 and 48 hours after punishment compared with the group receiving Scopolamine plus placebo (F (1, 77) = 11.20, p = 0.001).

The third recorded parameter - the number of entries into the dark chamber was not subjected to changes under the influence of drugs (Fig. 10).

The experiments showed the presence of nootropic, timoleptic and locomotor activity in BES, presented in the original combination. The predominant component among them, based on the results obtained, should be recognized as nootropic. Indeed, in the Porsolt test of “despair” behavior, BES did not show independent activity in relation to the main indicators - the time of immobilization and the time of active attempts. At the same time, BAS significantly improved the effect of the reference drug pyrazidol, the mechanism of action of which is dominated by the blockade of MAO A and the capture of serotonin and norepinephrine. It is believed that for truly nootropic drugs of the racetam class these effects are uncharacteristic. However, their optimization of the functioning of neurotransmitter systems, in contrast, is recognized.

Secondly, the effect of BAS on locomotor activity is comparable to the effects of the psychoanaleptic of phenamine only quantitatively, since the lack of cumulation when administered together indicates different mechanisms for the implementation of their effects. An important confirmation of this is the apparent absence in BES of the recoil syndrome characteristic of phenamin-like psychoanaleptics. On the contrary, after the introduction of BAS, the severity of the stable timoleptic effect increases with time.

Thirdly, in the spectrum of the pharmacological action of pyrazidol, a drug with pronounced antidepressant activity, there is a potentiation effect of phenamine, which turned out to be uncharacteristic for BAS.

Fourthly, when studying the effect of BAS on conditioned reflexes in the passive avoidance reaction test on the scopolamine amnesia model, the most convincing data were obtained that indicate the presence of nootropic activity in the drug. Indeed, the memory of the punishment in the form of electrodermal irritation was preserved after 24 and after 48 hours of observation in mice with both placebo and BES (25 mg / kg), while the protective effect of BAS against scopolamine was detected after 24 hours in both doses of the extract with a high degree statistical reliability: P = 0.027 for the parameter “latent period of the first entry into the hazardous chamber” and P = 0.001 for the parameter “total time spent in the light chamber”.

Claims (1)

The use of birch bark extract as a nootropic agent.

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