Tranquilizers: classification, a list of modern, day and non-receptible drugs. Tranquilizers (basic properties) What is anxiolitics nootropics

Anxiolitics (from Lat. anxietas. - alarming state, fear + Greek. lytikos. - capable of dissolving, weakening), or tranquilizers (from lat. tranquillo - soothe), or atraktiki (from Greek. ataraxia. - non-vulnerable) - psychotropic agents that reduce severity or overwhelming, fear, anxiety, emotional tension.

The appearance of the first tranquilizers belongs to the 50s of the XX century. Prior to that, alcohol, opium, bromides were used to correct the alarming states (from the beginning of the XIX century), barbiturates (from the beginning of the XX century) and others.

In 1952, during the search for central minelaxants, Meproamat (Meprotan) was synthesized. In the 60s, anxiolytic properties were discovered in a number of clinical studies (when taking high doses - 100-400 mg / day) in hydroxyzine (atarax) - one of the first anti-killed agents, antagonist H 1 -Histamine receptors, used in dermatology with In 1955, the first generation of anxiolyts also includes trimmosin (trioxazine, canceled in 1996), central cholinolitic Benactiisin (amizil), atypical anxiolitics Mebikar and benzoclidine (oxilidine).

Widespread use in medical practice, the drugs of the Anxiolytic drugs received from the 60s of the XX century, when the first tranquilizers appeared - benzodiazepine derivatives: Chlordiazepoxide (Librium, 1960) and Diazepam (Valium, 1962).

Historically, you can highlight 3 generations of anxiolyts:

First-generation anxiolists (Meproamat, hydroxyzine, Benactizin, etc.);

Second-generation anxiolytics (benzodiazepine drugs);

Anxiolitics of the third generation (buxpiron, etc.).

There are several classifications of drugs related to the Anxiolytic group: according to the chemical structure, the mechanism of action, pharmacokinetic and pharmacodynamic characteristics, etc.

By classification M.D. Mashkovsky Anxiolytic is represented by several classes of chemical compounds:

Benzodiazepine derivatives (benzodiazepines);

Snapped propaneiol carbamic esters (Meproamat);

Diffenylmethane derivatives (Benactisine, hydroxyzine);

Tranquilizers of different chemical groups (benzoclidine, buspid, mebikar, etc.).

According to D.A. classification Harkevich, according to the mechanism of action of anxiolytic, can be divided into the following groups:

Benzodiazepine receptor agonists (diazepams, phenazepam, etc.);

Agonists of serotonin receptors (buxpirons);

Substances of different types of action (Benactizin, etc.).

The mechanisms of anxiolytics are still not fully disclosed. The anxolytic effects manifests itself by reducing the excitability of subcortical areas of the brain (limbic system, thalamus, hypothalamus), responsible for the implementation of emotional reactions, inhibition of the interaction of these structures with the cerebral cortex, as well as the oppression of polysinactic spinal reflexes.

In the neurochemical aspect, different anxiolitics differ in action features. The effect on the noradreengic, dopaminergic, serotonergic systems is expressed in them in relatively weak degree (The exception is buxupiron). The effects of benzodiazepines are mediated by the impact on the brain gamingric system.

Currently, the leading position of the Anxiolytics group is continued to occupy the benzodiazepine derivatives. Most anxiolithic benzodiazepine structure are 1,4-benzodiazepine derivatives. The basis of the chemical structure of benzodiazepines consists of a benzene ring connected to a seed heterocyclic ring containing two nitrogen atoms (diazepine) in positions 1 and 4. All benzodiazepine derivatives used in the clinic also have a second benzene ring attached to carbon at position 5. For the manifestation of activity It is essential to the presence of a halogen or nitro group in the 7 position. Some compounds of a group of benzodiazepines contain 1,5-benzodiazepine residue in the molecule (hlobazam) or 2,3-benzodiazepine (tophizobam).

Due to the easy replaceability of radicals in various provisions in the benzodiazepine molecule, more than 3 thousand compounds were synthesized and studied, of which several dozen are registered in various countries as medicines.

In accordance with substituents in the diazepine ring, benzodiazepine can be classified as follows:

2-keto benzodiazepines contain a keto group at a carbon atom in position 2 (diazepams, Clorazhepat, Flurazhepam *, etc.);

3-hydroxy-benzodiazepines contain a hydroxy group with a carbon atom in position 3 (OccAZPAM *, Lorazepam, Wecezapam *);

Triazolobenzodiazepines contain a triazole ring connected to a diazepine ring through a nitrogen atom in position 1 and a carbon atom in position 2 (alprazolam, triazolas *, estazolam *).

Perhaps the presence of other additional substituents in the structure of benzodiazepine, for example, the imidazo group (Midazolas *), etc.

Electrophysiological studies conducted in the 60-70s. XX century, showed that benzodiazepines enhance the gamkerygic transmission to the central nervous system. The mechanism of action of benzodiazepines has become understood after in 1977, with the help of the radioligand method in the human and animal brain, the places of specific binding of benzodiazepines were found, so-called Benzodiazepine receptors (BD receptors). Further in experiments in vitro. and in vivo. A correlation was revealed between the ability of various benzodiazepines to communicate with these sites and their pharmacological activity. Methods of autoradiography and electron microscopy were shown that the BD receptors are localized mainly in the Sinaps of the CNS, mainly in postsynaptic membranes. The heterogeneity of the BD receptors, which are presented in the mammalian brain at least two subtypes - database 1 and database 2.

After the detection of the specific binding places of benzodiazepines began the search for endogenous compounds interacting with the BD receptors, the so-called. Endogenous ligands. As an endogenous bd receptor ligands, a large number of compounds are considered: peptides, purines, nicotinamide, hypoxanthine, beta carbolines, diazepam binding inhibitor (DBI), etc., but the nature of the endogenous ligand of the BD receptors is not clarified.

Currently, benzodiazepines are considered to interact with specific benzodiazepine receptors (are agonists of these receptors), part of the postsynaptic GABC and -receptor complex in the limbic brain system, thalamus, hypothalamus, ascending activating reticular formation of the brain barrel and inserting neurons of lateral horns spinal cord. Benzodiazepines increase the sensitivity of GAB-receptor to the mediator (GAB), which causes an increase in the opening frequency in the cytoplasmic membrane of channel neurons for incoming currents of chlorine ions. As a result, the braking influence of the GABA and the oppression of interneuronous transmission in the respective divisions of the CNS occurs.

The effect on the GAMK transmission is the main mechanism of action of benzodiazepine anxiolytic. Other media systems of the brain can play a certain role in the implementation of the effects of benzodiazepine anxiolyts.

Benzodiazepines have a wide spectrum of pharmacological action, including anxiolytic, sedative, sleeping pills, miorelaxing, anticonvulsant, amnesic, etc.

The effects of benzodiazepines are due to the influence of various departments of the CNS: the almond complex of the limbic system (anxiolytic), the reticular formation of the brain barrel and nonspecific thalamus kernels, hypothalamus (sedative and sleeping bag), hippocampus (anticonvulsant).

The main effect characteristic of all drugs united in the Anxiolytic group and determine the use of these funds with all types anxiety disordersIs an anxolytic (anti-time). Anxiolytic action is manifested by a decrease in anxiety, fear (antifobic effect), emotional tension.

Sedative (soothing) action is manifested by a decrease in psychomotor excitability, daily activity, decrease in the concentration of attention, reducing the reaction rate, etc.

Sleeping (hypnotic) effect is expressed in facilitating the onset of sleep and increasing its duration. The inhibitory effect of tranquilizers on the central nervous system contributes to the mutual strengthening effects of sleeping pills, anesthetic and analgesia.

Miorolaxizing activity (relaxation of skeletal muscles) is mainly due to the braking of polysinactic spinal reflexes. Benzodiazepines can also provide direct depressing effect on motor nerves and muscle function. The mineral effect when using tranquilizers is often a positive factor for removing the voltage, excitation, incl. Motor, but may also limit the use of drugs in patients whose work requires a quick mental and physical reaction. It should be borne in mind that a miorylaxing effect can manifest itself with a feeling of lethargy, weaknesses, etc.

Anticonvulsant action is manifested in suppressing the spread of epileptogenic activity arising in epileptogenic foci in the crust, thalamus and limbic structures. Anticonvulsant action is associated not only with the impact on the GABA and -receptor complex, but also due to the effect on potential-dependent sodium channels.

Amnesian action (the ability to cause amnesia) is manifested mainly in parenteral use (diazepams, muscolas *, etc.). The mechanism of this effect is not yet clear.

In the spectrum of action of some tranquilizers sometimes allocate additional effects, incl. Vegetable stabilizing. The growing stabilizing effect is associated with the normalization of the functional activity of the vegetative nervous system. Clinically, this effect can be expressed by a decrease in the vegetative manifestations of anxiety (the instability of blood pressure, tachycardia, sweating, disruption of the function of the tract and other). Severe vegetotropic effects possess tofizopas, diazepams, guides, etc.

Benzodiazepine derivatives may exhibit all pharmacological properties characteristic of this group, however, the severity and ratio of effects in different benzodiazepines may be different, which causes the characteristics of the clinical use of individual drugs.

According to the characteristics of the clinical action, benzodiazepine anxiolitics can be divided into 3 groups:

one). Benzodiazepines with a predominance of anxiolytic action.

2). Benzodiazepines with a predominance of a sleeping pills.

3). Benzodiazepines with a predominant anticonvulsant.

Penazepams have a pronounced anxiolytic effect (by anxiolytic activity, many benzodiazepines are exceeded, incl. Diazepams), diazepams, lorazepam, alprazolam, and others. Anxolytic effect of chloridiazide, bromazepama, guideazepama, hlobazama, oxazepama, etc.

The sedative-hypnotic effect is especially expressed in nitrazempama *, flunutrazepama *, flurazhepama *, Tepezapama *, triazolam *, Midazolam *, Estazolam * et al. And they are used mainly as sleeping pills (see).

Anticonvulsant properties are characteristic of cloneazepama, diazepam, as well as (to a lesser extent) for nitrazempama * et al.

Miorolaxizing activity is characteristic of diazepama, chlordiazepoxide, Lorazepam, Tetrazepama, etc.

For some anxiolytic, a pronounced anxiolytic effect is characterized by relatively weak mioroxing and sleeping pills (tofizopams, medazpes, etc.), and therefore they are more convenient for use in daytime clocks (so-called daytime tranquilizers).

Benzodiazepine derivatives differ in the peculiarities of pharmacokinetics, which is also taken into account when appointing these drugs. By duration of action (taking into account the effect of active metabolites), benzodiazepines can be classified as follows:

Long action (t 1/2 - 24-48 h): diazepam, chlordiazepoxide, etc.;

The average duration of action (T 1/2 - 6-24 h): Alprazolam, Oxazepam, Lorazepam, etc.;

Short action (t 1/2 - less than 6 hours): Midazolas * et al.

All benzodiazepines are lipophilic connections. The lipophilicity of different substances of this group varies more than 50 times, the most lipophilic from benzodiazepines are diazepams and Midazolas *.

When taking inside, benzodiazepines are well absorbed from the gastrointestinal tract, mainly from the duodenum (absorption depends on several factors, incl. From lipophilism). The most quickly absorbed by diazepams and triazoles *, the least fast - oxazepam, Lorazepam. Antacids can reduce the speed (but not the degree of suction) of some benzodiazepines, incl. Diazepam and chlordiazepoxide. After intramuscular administration, benzodiazepines are absorbed slower than when taking inside (the exception is the Lorazepam and Midazolas *, which at the I / M administration are absorbed quickly).

The time to achieve the maximum concentration in the blood plasma after one-time reception for different LS varies from 30 minutes to several hours. The equilibrium concentration in the blood in the course reception of benzodiazepines is usually achieved within a few days after the start of therapy (for benzodiazepines with a short and mid-high-alignment period) or within 5 days - 2 weeks (for preparations with a long half-life). Benzodiazepines and their metabolites are characterized high degree Binding of blood proteins varying from 70% (Alprazolam) to 98% (diazepam).

High lipophilicity causes the penetration of these drugs through the BGB and other biological barriers, as well as a significant speed of redistribution from the CNS in tissue (adipose tissue, muscle). The volume of the distribution of benzodiazepines is quite high.

The primary metabolism of benzodiazepines occurs in the liver. The exceptions are Dicalia Clossepat and flurazheps *, which are quickly metabolized into the gastrointestinal tract and do not fall into systemic bloodstream in clinically significant quantities. The action is provided by their active metabolites, which are subjected to biotransformation in the liver. Most benzodiazepines are subjected to microsomal oxidation in the liver, mainly by N-demethylation or hydroxylation to active or inactive metabolites. Then the metabolites are conjugated or further biotransformation.

In the process of metabolism, many benzodiazepines formed the same active metabolites, some of them are used as independent drugs (oxaispames, etc.). The duration of the therapeutic effect for benzodiazepines having active metabolites is determined not by 1/2 of the starting material, and T 1/2 active metabolites. For example, T 1/2 of the Deshethyldiazepam (NORDIAZEPAMA), which is an active chloridiazide metabolite, diazepam and chloride diazepath, is, by one data, more than 30-100 hours, from another 40-200 hours, which significantly exceeds the semi-exploration periods.

Some benzodiazepines do not form active metabolites - Lorazepam, oxazepam, themezapam * et al. And are exposed only to the conjugation process under the action of glucuronyltransferase with the formation of glucuronides.

Benzodiazepines (and their metabolites) are derived mainly through the kidneys in the form of conjugates, less than 2% - unchanged, a small part - through the intestine.

Some pharmacokinetic parameters of benzodiazepines depend on age. So, in elderly patients can increase the volume of distribution. In addition, in the patients of elderly and children can be eliminated by half-life.

The appearance and duration of the effects for benzodiazepine anxiolitics are not always associated with their half-life, but in case reception, these parameters correlate largely. When receiving repeated doses of benzodiazepines with a durable T 1/2, the cumulation of the drug itself and / or its active metabolites occurs. The effect of the afterest of drugs (diazepam, etc.) is associated with this. The accumulation of benzodiazepines with a short or mid-high-rise half-life is usually minimal, and they are quickly derived from the body after the end of therapy.

Spectrum clinical use Anxiolyts are mainly connected with their anti-tested effect. Benzodiazepines are used for all types of anxiety disorders (they can be shown to treat alarming states or for short-term troubleshooting symptoms).

In psychiatric I. neurological practice Anxiolytics are used in the treatment of neurosis, psychopathy, neurosis-like and psychopath-like states, accompanied by anxiety, fear, increased irritability, emotional voltage. To relieve anxiety-phobic disorders ( panic attacks et al.) Effective drugs with the maximum expressed anxiolytic and antifobic effect - Alprazolam, Lorazepam, and phenazepam. Some benzodiazepine anxiolitics are used to relieve anxiety syndrome under endogenous mental illness, incl. in schizophrenia (as auxiliary means complex therapy) - diazepams, phenazepam, etc.

With acute states, for example, in order to relieve pronounced psychomotor excitation, the parenteral administration of benzodiazepines (diazepams, phenazepams, etc.) is effective.

With acute alcohol abstinence of anxiolytic (diazepams, oxazepams, phenazepams, chlordiazepoxide, etc.) are used as part of comprehensive therapy to facilitate symptoms such as excitation, nervous stress, anxiety, anxiety, tremor, as well as to reduce the likelihood of development or signs, in t. h. hallucinations arising acute delirium.

In case of sleep disorders, benzodiazepines are used, along with an anxiolytic, pronounced sleeping reaction (nitrazempams *, flunutrazepams *, Triazolas *, templazapam *, etc.). They remove emotional tension, reduce the alarm, anxiety and contribute to sleep offensive. Application in disabilities of sleep of such benzodiazepines such as diazepams or phenazepams, it is advisable in cases where the insomnia is combined with day alarm and it is desirable that an anxiolytic action continues throughout the day.

Benzodiazepines with pronounced anticonvulsant action It can be effective in the treatment of epilepsy, epileptic status (clonazepam, diazepams, etc.), nitrazempam * - with some forms of convulsive seizures, especially in children (see).

Benzodiazepines, like other anxiolitics, found wide application In many areas of medicine: in cardiology, anesthesiology and surgery, dermatology, etc.

Some benzodiazepines with a pronounced mioronexizing effect (diazepams, chlordiazepoxide, etc.) are shown in spastic conditions associated with the lesion of the head or spinal cord, etc.

Benzodiazepines are used for premedication on the eve and immediately before operational interventions and endoscopic procedures for input narcosis, in atalagesia, in combination with analgesics (flohutrazepams *, Midazolas *, diazepam, etc.).

The use of some anxiolyts healthy people It can be justified with acute reactive stressful states in extreme situations (fire, industrial catastrophe, earthquake, etc.). It should be borne in mind that anxiety or tension associated with everyday stress is not an indication for the purpose of anxiolytic, therefore, they should not be prescribed them for any stressful states, in particular with the reactions of grief or somatic diseases.

The main contraindications to the purpose of benzodiazepines are individual hypersensitivity, severe liver failure, severe myasthenia, glaucoma, expressed respiratory failure, ataxia, suicidal inclinations, narcotic or alcohol addiction (except for the treatment of acute abstinence syndrome).

Avoid reception of benzodiazepines during pregnancy (especially in the first trimester) and during breastfeeding period.

Benzodiazepines easily pass through the placenta. There is evidence that chlordiazpexide and diazepams increase the risk of congenital malformations when prescribed in the first trimester of pregnancy. Other drugs of this group may also increase this risk, therefore, to the appointment of benzodiazepine drugs during pregnancy, it should be approached very carefully and apply them only in the absence of an alternative, comparing a possible risk to the fetus and benefit for the mother.

When appointing benzodiazepines (clonazepams, diazepams, etc.) during pregnancy, women, patients with epilepsy, should be borne in mind that there are reports of increasing the frequency of congenital defects in children whose mother took anticonvulsant drugs during pregnancy, but the causal relationship between these The facts have not yet been established. On the other hand, in women who take anticonvulsant preparations (for example, clonazepams), their abolition before or during pregnancy is possible only in cases where epileptic seizures are weak and rare in the absence of treatment and if the probability of epileptic state and cancellation symptoms are estimated as low.

The use of benzodiazepine derivatives in the third pregnancy trimester (especially in recent weeks) can lead to the accumulation of the drug in the tissues of the fetus, and as a result, to the oppression of the CNS in newborns. At the same time, muscle weakness, hypothermia, inhibition of breathing, impaired renovation reflex may be observed in newborns.

Long-term intake of benzodiazepines during pregnancy, incl. In the later stages, it can lead to the formation of the physical dependence and development of symptoms of cancellation in a newborn.

With caution (only on strict indications), benzodiazepines are used during the period of generic activity, for example, parenteral administration of diazepam with premature birth or premature placenta detachment. Diazepams in low doses, as a rule, does not adversely affect the fetus, however, the use of high doses can cause newborn heart rate disruption, lowering pressure, attacks of suffocation, muscle weakness, hypothermia, etc. Symptoms.

Since benzodiazepines penetrate into breast milk in significant quantities, the means of this group should not be used with nursing mothers. In newborns, the metabolism of benzodiazepines is slower than in adults, as a result of which these LS and their metabolites can accumulate in the body and cause a sedative effect. In this case, difficulties are possible when feeding and weight loss in newborns.

In therapeutic doses, benzodiazepines usually do not affect the respiratory function, do not change the blood pressure. However, patients with obstructive lung diseases, with apnea syndrome during sleep, etc. Against the background of taking these drugs, the state may worse.

The parenteral administration of benzodiazepines, especially the patients of elderly and old age, can lead to breathing disorders (apnea) and the functions of the cardiovascular system (hypotension, bradycardia, up to the heart stop).

It is not recommended to use benzodiazepines as the only means in the treatment of anxiety in combination with depression or with a pronounced depression, because Suicidal attempts may be possible (benzodiazepines can enhance the manifestation of depression). However, some of the anxiolytics of benzodiazepine structure (Alprazolam, Lorazepam, Oxazepam) are effective in the treatment of anxiety on the background depressive states Various genes (as a rule, in combination with antidepressants).

Since most benzodiazepines are subjected to biotransformation in the liver, with a violation of its function, the duration of the therapeutic effect of these drugs may vary, may occur serious side effects. In this regard, it should be particularly safe when prescribing benzodiazepines to patients with impaired liver function.

The use of anxiolytics in children and adolescents under 18 is justified only in exceptional cases, with clearly reasonable indications, while the duration of treatment should be minimal.

Patients of elderly and senile age, weakened patients, children (especially small) are usually more sensitive to neurotropic action of benzodiazepines. In particular, patients over 65 should avoid systematic reception of benzodiazepines (especially long-term action), because Reception of these LS can lead to undesirable consequences in the form of an excessive sedative effect, dizziness, orientation disorders and coordination of movements. This may be the cause of falling patients and related fractures.

Adverse side effects when taking benzodiazepines are signs of oppression of the CNS, incl. drowsiness during daytime, lethargy, muscle weakness, dulling emotions, headache, dizziness, ataxia, etc. It is possible to violate cognitive functions (for example, with long-term reception of diazepam, a phenazepama).

Due to the reduction of the velocity of psychomotor reactions, the weakening of the concentration of attention should be cautious to prescribe anxiolitics outpatient, incl. Patients whose work requires a fast mental and physical reaction, and is also associated with an increased concentration of attention (drivers of vehicles, etc.).

When receiving anxiolytic agents of benzodiazepine rows, paradoxical reactions (acute arousal, anxiety, hallucinations, nightmarish dreams, fury attacks, inadequate behavior) are possible, which are more often manifested in children, patients of senile age and mentally ill patients. In the occurrence of paradoxical reactions, the drug should be canceled immediately.

After receiving some, mostly long-term drugs (for example, diazepams), a follow-up syndrome (muscular weakness, reduction of health, etc.) is possible.

The use of anxiolytic can lead to the development of addiction (reducing the effect during long-term reception), as well as to the formation of drug dependence (physical and / or mental) and the occurrence of cancellation syndrome. The risk of dependence increases with long-term use (more than 6 months), especially in high doses, as well as in patients with medicinal and alcohol dependence in history.

With a sharp abolition of the drug against the background of drug addiction, cancellation syndrome (tremor, cramps, vomiting, increased sweating), in severe cases - depersonalization, hallucinations, epileptic seizures (sharp cancellation during epilepsy).

It should be remembered that the treatment with anxiolyts can be carried out only under the supervision of the doctor. When prescribing benzodiazepines for the treatment of anxiety disorders, the principle of gradual increase in the dose should be observed from minimally effective to optimal to obtain the therapeutic effect (acute states). The course of treatment should be as short as possible, after which a repeated assessment of the patient's condition is needed to decide on the need to continue therapy. In connection with the possibility of developing addiction and the appearance of drug dependence, the WHO's conciliation commission (1996) does not recommend using the drugs of benzodiazepine series continuously more than 2-3 weeks. If you need long-term treatment (several months), the course should be carried out according to the method of intermittent therapy, stopping the reception for several days, followed by the appointment of the same individually selected dose. Cancellation should be carried out by gradually reduce the dose to reduce the risk of cancellation syndrome.

In case of treatment with anxiolyts, it is necessary to take into account the possible interaction of drugs of this group with other drugs. Anxiolytics potentiate the effects of other means of depressing CNS (narcotic analgesics, anesthesia, sleeping pills, neuroleptics with severe sedative effects, antihistamines with a pronounced sedative effect), Miorlaxants, etc.

When receiving anxiolytics, alcoholic beverages are unacceptable, since alcohol enhances the depressing effect of LS of this group on the CNS (which may be accompanied by severe side effects, incl. Loss of consciousness, inhibition of breathing), in turn tranquilizers enhance the toxic effect of alcohol on the central nervous system. With simultaneous use with alcohol, in addition to the amplification of the inhibitory effect on the CNS, paradoxical reactions (psychomotor excitation, aggressive behavior, a state of pathological intoxication) are possible.

The simultaneous intake of benzodiazepines with other means depressing the central nervous system, as well as alcohol can lead to overdose and life-threatening consequences (in case of serious overdose, medical intervention is required).

The symptoms of the anxiolytics overdose may be the oppression of the central nervous system of varying degrees of severity (from drowsiness to coma), incl. Pronounced drowsiness, lethargy, weakness, reduced muscle tone, ataxia, in more severe cases - long-term confusion of consciousness, oppression of reflexes, coma, hypotension, and inhibition of breathing are also possible. With benzodiazepines intoxication, it is necessary to cause vomiting, the use of activated carbon, washing the stomach through the probe (if the patient is unconscious), symptomatic therapy, is necessary to monitor vital functions, in / in the introduction of liquids (to enhance the diurea), if necessary - IVL. Hemodialysis in the overdose of benzodiazepines is ineffective.

The specific antagonist of benzodiazepine receptors is fluumazenyl - 1,4-benzodiazepine derivative with high affinity to benzodiazepine receptors. It competitively blocks benzodiazepine receptors and eliminates or reduces the severity of the central effects of substances exciting these receptors, but does not interfere with the action on the central nervous system with the depressing effect (barbiturates, opioids, etc.). The use of fluumazenil as a specific antidote in the overdose of benzodiazepines is possible only in the hospital. It should be borne in mind that fluumazenyl is used as an additional, and not as the only means. When in / in the introduction of fluumazenyl acts quickly, but shortly (the action of all benzodiazepines lasts longer), therefore it is possible to return the symptoms of overdose. In addition, the development of epileptic seizures is possible (especially in patients who have taken benzodiazepines together with tricyclic antidepressants, in patients with epilepsy).

Despite the fact that benzodiazepines occupy a leading position according to the degree of study and latitude of application, other anxiolytics are also used in medical practice.

So far, Benzoclidine has not lost its value. Benzoclidine reduces the activity of cortical neurons and inhibits the activity of the reticular formation of the brain stem, lowers the excitability of the vascular center, improves brain circulation. It is used in the treatment of anxiety disorders, incl. Anxious depressive states (especially expressed and related to the insufficiency of cerebral circulation). Especially shown by the elderly patient with atherosclerosis with cerebral disorders, arterial hypertension, paroxysmal tachycardia.

Return of interest in the hydroxyzine is associated with the peculiarities of its pharmacological action. Hydroxyzine is an antagonist of central M-Holino and H 1 -Histamine receptors. A pronounced sedative and moderate anxiolytic effect is manifested due to the oppression of the activity of some subcortical structures of the central nervous system. Hydroxyzine is characterized by a fairly rapid development of anxiolytic action (during the first week of treatment), the absence of an amnesian effect. Unlike benzodiazepines, with long-term use, hydroxyzine does not cause addiction and dependence, no cancellation syndromes, "returns" are not marked. In addition to use in the treatment of anxiety disorders, incl. In psychosomatic diseases, it is used for premedication, the relief of the abstinente alcohol syndrome, as well as with itchy dermatoses.

Benactiisin (diphenylmethane derivative) is significantly different from other anxiolytics, the anxiolytic effect of which is due to the reversible blockade of central M-cholinoreceptors. Due to the pronounced influence on the central cholinoreactive structures, Benactiisin belongs to the group of central cholinolithics. Its influence on the CNS is manifested by the soothing effect, the oppression of the convulsive and toxic effect of anticholinesterase and cholinomimetic substances, the strengthening of the barbiturates and other sleeping pores, analgesics, etc. Currently due to the presence of effective tranquilizers, as well as due to undesirable side effects, associated with an atropine-like action (dryness in the oral cavity, tachycardia, mydriasis, etc.), Benactive is practically not used as an anxiolytic.

The propanediogen derivative (Meproamat) of influence on benzodiazepine and cholinergic receptors does not. Its anxiolytic effect is associated with the oppressive influence on the various departments of the CNS, including the Talamus and the limbic system, the minelaxing effect is due to the braking of excitation transmission in the field of inserting neurons of the side horns of the spinal cord, thalamus and hypothalamus. In addition to the treatment of anxiety disorders, Meproamat is used in menopausal and premenstrual syndromes. It is less effective than benzodiazepines, and currently has limited use.

Representatives of the third-generation anxiolyts are buspillary, oxymethylpyridine succinate (mexidol) and others. Anxiolytic effect of mexidol is associated with its modulating effect on the membranes, incl. GAMK A -receptor complex, and is manifested by improving the synaptic transmission.

The mechanism of the buspine action is not fully found. Buspirone is a partial agonist of serotonin receptors, has a high affinity for serotonin subtype receptors 5-NT 1A. Reduces the synthesis and release of serotonin, the activity of serotonergic neurons, incl. In the dorsal core of the seam. In addition, it selectively blocks (antagonist) of pre- and postsynaptic D 2 - phosic receptors (has moderate affinity) and increases the rate of excitation of dopamine neurons of the mid-brain. Some evidence suggests the existence of an influence on other neurotiator systems. Buspirone is effective in the treatment of mixed anxious-depressive states, panic disorders, etc. Anxiolytic effect develops gradually, manifests itself after 7-14 days and reaches a maximum after 4 weeks. Unlike benzodiazepines, Buchariron does not have a sedative action, a negative effect on psychomotor functions, does not cause tolerance, drug dependence and symptoms of cancellation, will not potentiate alcohol.

In addition to drugs belonging to the anxiolytic group, the anti-theft effects have preparations of other pharmacological groups: some beta-adrenoblays (propranolol, oxprenolol, acebotolol, thymolol, etc.), alpha adrenomimetics (clonidine). Thus, propranolol is effective in the treatment of the states of anxiety associated with the hyperreactivity of the sympathetic nervous system and accompanying the significant severity of somatic and vegetative symptoms, clonidine has the ability to reduce the somadegentic manifestations with the abstinence syndrome of opium drug addiction.

In the treatment of anxiety disorders, incl. Under intrusiveness, panic disorders, some antidepressants are shown (see). With severe disturbing disorders, the pronounced effect is given separate preparations from a group of neuroleptics (see).

Currently, an intensive search for new drugs with anxiolytic effect continues and at the same time safe and efficient than the existing drugs. Screening benzodiazepine derivatives is aimed at identifying more selectively active drugs with a maximum expressed anxiolytic effect with a minimum of side effects. The search is also carried out among substances affecting serotonergic transmission, exciting amino acid antagonists (glutamate, aspartate), etc.

Preparations

Drugs - 1329 ; Trade names - 99 ; Active substances - 23

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Citation:Buldakova N.G. Antidepressants and anxiolytics: advantages and disadvantages // RMW. 2006. №21. P. 1516.

Over the past decades, psychopharmacotherapy has confidently stepped forward, new drugs appeared for the treatment of mental illness. Currently, questions are extremely relevant to the selection of psychotropic drugs (PS) for patients not only a psychiatric clinic, but also of general studies. This is due to the wide prevalence of disturbing and depressive states among the population (in Russia to 6-7%) and its steady growth, frequent combination of mental pathology with somatic, in connection with the need to apply the PS doctors of various specialties. They are, and not neurologists and psychiatrists, prescribe 2/3 of all PS. As a result, according to WHO, about 1/3 adults of developed countries are taking psychopharmacological drugs (in the absence of hypodiagnosis, this indicator could be even higher).

Two classes of PS - antidepressants and anxiolitics deserve greater attention, due to their efficiency in various nosologies, the possibility of minimizing unwanted effects, making therapy as safe as possible, ease and flexibility of application, relatively good learning, and therefore more frequent destination.
Antidepressants are the most actively developing PS Group, their number is currently calculated by many dozens. Antidepressants or TimoNalelets improve the pathologically reduced mood, as well as the general condition of patients by reducing the depressed by the depression of ideasotor and somato-vegetative violations. Moreover, these drugs do not increase normal mood and do not show psychostimulating action. Some antidepressants have antitrusive, sedative, hypnotic, anti-foot properties.
Exist various classifications Antidepressants for the chemical structure, the mechanism of action, on spectra of psychotropic activity, depending on the scope and risk of side effects.
According to the mechanism of action, antidepressants are divided into: monoaminoxidase inhibitors (MAO), and, consequently, the peeing deamination of norepinephrine and serotonin (mainly hydrazine derivatives, for example, niamide), and blockers of the reverse neural seizure of these mediators (so-called tricyclic antidepressants (TCCA) - amitriptyline , Northriptyline, imizine, doxypin, clomipramine, imipramine, etc.). These are first generation preparations, effective with respect to a wide range of depression - from severe to subsidommal.
The second generation preparations are synthesized, according to the mechanism of action differing from the above-described "typical" antidepressants. They are called "atypical", and they include selective inhibitors of serotonin inverse seizure (SIRES) - fluoxetine, paroxetine, cytalopram; Selective stimulants of serotonin reverse seizure (CRES) - thianeptin; Reversible inhibitors of monoaminoxidase type A (OIMAO-A) - pyrazidol, Moklobemide; Selective Blockers of the reverse seizure of norepinephlation (broken) - Maprotilin, Mianserin; Selective Blockers of the presynaptic capture of dopamine - amineptin, bupropion. Preparations of this group have activity against depressions of light and medium degrees of gravity.
Due to the difference in the chemical structure and the mechanism of action, antidepressants are divided into the field of application (according to the classification of Acad. Ramna, prof. A. B. Smelevich).
Preparations of recent generations refer to the means of the first row - for use in general student practice. They have election psychotropic activity, good profiles on tolerance and safety, low risk of unfavorable interaction with somatotropic drugs, minimal toxic effect on the fetus, as well as simplicity in application. All this became possible due to an increase in the specificity of the biochemical action of these antidepressants or the maximum reduction of their influence on the receptors with which the development of side effects is associated. The TCC and IMAO refer to the means of the second row - for use in specialized psychiatric medical institutions. They are prescribed mainly in severe forms of depression, when despite undesirable phenomena arising from treatment, their powerful psychotropic effect is necessary.
However, the clinical use of antidepressant cannot be based only on general RecommendationsThe goal when choosing a drug is the individualization of the patient's treatment scheme. The age should be taken into account, the nature of the course of the disease, concomitant somatic pathology and related treatment, features of the therapeutic effect of a means, including the breeding, individual sensitivity to PS, patient's personal qualities, etc. In addition, in general medical practice, when treatment must be carried out in Ambulatory conditions, in the form of long courses, when a patient is a working person, it is impossible not to pay attention to the frequency of reception, compinlation and side effects.
Preference is given, of course, modern means With the frequency of application not more than 1-2 times per day, which does not significantly violate the routine of patients. The coherence of the actions of the doctor and the patient is indisputably important, since the implementation of recommendations is the key to the success of the therapy.
The most pronounced side effects possess the TCC. Due to their strong cholinolitical effect, dryness of mucous membranes, constipation, urination delay, accommodation violations, changes in heart rate (is precisely therefore glaucoma adenoma, heart adenoma, violations of the heart are contraindications to the purpose of the TCA). In addition, bradycardia, arterial hypotension and behavioral toxicity phenomena, such as a breakdown of sleep-wake cycle and daily drowsiness, disruption of fine coordination of movements, reducing attention, memory, spatial orientation. It is in preparations of the first row above the risk of cardiotoxic, hepatotoxic, neurotoxic actions, as well as influence on sexual functions. In addition, the TCC interacts in an undesirable way with many somatotropic drugs (thyroid and steroid hormones, some antiarrhythmic drugs, heart glycosides, etc.). It is also necessary to remember the drug dependence and cancellation syndrome.
Anxiolitics (from Lat. Anxius - "alarming" and Greek. Lysis - "dissolution"), attractive or tranquilizers (from lat. Tranquillium - "Calm") appeared in the pharmaceutical market a few later antidepressants. In the 60s. The XX century, the first drugs of this group were introduced into clinical practice, the first preparations of this group - Meproamat, chloridiazepoxide, diazepam, after which more than 100 active compounds were synthesized and their improvement and search for new more efficient were improved. Among the PS tranquilizers are practically the most widely used drugs and in the hospital, and especially in outpatient practice.
There are various classifications of anxiolyts:
1) by sedimentation of the sedative effect:
- with a pronounced sedative (hypnosened) effect - gindarin, amikside, chloridiazepoxide, phenazepam, biennaceasin, some derivatives of benzodiazepine et al.;
- with a minor sedative action (alprazolam, benzoclidine, oxazepam, etc.);
- "daytime" tranquilizers with the prevailing actual anxiolytic effect and the minimum sedimentation of sedative or even with a slight stimulating effect (guides, Mebikar, Prazadam);
2) by chemical structure:
- benzodiazepine derivatives (long-acting - diazepams, phenazepams, cinasapam; medium duration - chlordiazepoxide, laureplates, nosheps; short action - Midazolam, triazola);
- Diffenylmethane derivatives (Benactisine, hydroxyzine, deprola) and 3-methoxybenzoic acid (trioxazine);
- ethers of substituted propanediola (Meproamat);
- Hinuclidine derivatives (oxylidine) and Azaspiriodekandion (buxpiron);
- barbiturates, as well as derivatives of pyridine and pyrrolone series and phytopreparations;
3) by mechanism of action (the most important classification in terms of understanding of pharmacodynamics and the essence of side effects):
a) according to D.A. Harkevich: benzodiazepine receptor agonists, agonists of serotonin receptors and preparations of different types of action;
b) on T. A. Voronina and S. B. Senenin:
- from traditional anxiolytics - direct agonists of the GAMK-benzodiazepine receptor complex (benzodiazepine derivatives) and preparations of various mechanisms of action (Mebikar, Benactisine, oxylydine, etc.);
- from new anxiolytics - partial agonists of benzodiazepine receptor (BDR), substances with different tropiness to DRA and GAB-receptor subunits; endogenous modulators of the GAMK-benzodiazepine receptor complex; glutamanthergic and serotonergic anxiolitics; NMDA receptor antagonists and others;
4) on the prevailing effect: actually tranquilizers (diazepams, etc.), sleeping pills (nitrazempam, mussels, kolpidam), sedatives (combined preparations with barbiturates, phyto-preparations, etc.).
The range of use of anxiolytics in clinical practice is very wide. They are used to eliminate the feeling of fear, anxiety, emotional tensions, increased irritability, for the treatment of complex syndromes (anxious-depressive, affective-delusive, etc.), post-traumatic stress disorders and cancellation syndrome, specific states (panic, obsessive-compulsive, social and isolated phobia, postpartum depression, adaptation disorders, etc.). Tranquilizers have hypnotic, minelaxing, vegetative stabilizing, amnistic and anticonvulsant effects. They are often used in general general practices (with headaches, psychosomatic diseases, hypertension, premenstrual voltage syndrome, for premedication, etc.).
The positive feature of anxiolyts is the lack of severe side effects, good tolerability and safety of their use due to the lack of adverse effects on the majority functional systems organism and interaction with somatotropic drugs. Due to the unfavorable influence on the intrauterine fruit, anxiolytic is contraindicated during pregnancy, as well as lactation.
The main side effects are hyperseration, minelaxation, "behavioral toxicity" (occurs in 15.4% of the receiving anxiolytics and manifests itself in basically impaired attention and coordination of movements), "paradoxical" reactions (more often in the form of increasing aggressiveness and enhancing).
Most often benzodiazepine, in addition, can cause arterial hypotension, dizziness, dry mouth, dyspepsia, increasing appetite and food intake, dysuria, violation of sexual functions. The possibility of abuse and the occurrence of dependence, and the risk of the latter is directly proportional to the duration of treatment. In this regard, according to WHO recommendations, the course of therapy benzodiazepines should not exceed two weeks.
Also, you can not forget about the cancellation syndrome. Its manifestations are dizziness and headache, irritability and anxiety, nausea and metal taste in the mouth, sweating and tremor, pain in muscles and violations of vision, sensitivity impairment and much more. Usually it proceeds Nazel.
Tolerance, typical of benzodiazepines, which is typical of the reducing effect of the drug during its reinforcement.
Another negative point when using PS data is the manifestation of all their properties at the same time. However, their hyposhedal, mineral and amnetic effects significantly reduce the quality of the life of patients receiving the treatment of outpatient. In addition, according to the results of research in the laboratory of the pharmacological genetics, the Research Institute of Pharmacology of the RAMS under the leadership of Academician of the RAMS, Professor S.B. Senenina revealed that the effects of benzodiazepine tranquilizers in each patient are implemented in different ways. It depends on the genetically deterministic individual response to the emotional and stress impact, which stimulates some people and morally "paralyzes" others. Benzodiazepines, having an anxiolytic effect on individuals unstable to stress, cause drowsiness, inhibition of individuals with active behavior. Therefore, the task of leading pharmacologists has become the development of a drug, which is not different from benzodiazepines, effectively affects passive individuals properly, but does not disorganize active.
This preparation is created. Afobazol, developed in the Research Institute of Pharmacology of the RAM, has already begun to be produced by Masterlek CJSC. Patents received on Afobazole Russian Federation, USA, Europe and Japan.
Aphobazole is an original anxiolytic, is not a benzodiazepine receptor agonist, according to a chemical structure - 2 [-2- (morpholino) -ethyl] -thio-5-ethoxybenzylimidazole dihydrochloride, a derivative of 2-mercaptobenzimidazole. The drug prevents the development of membrane-dependent changes in the GAMK-benzodiazepine receptor complex observed in the formation of emotional-stress reactions and leading to a decrease in the availability of a benzodiazepine receptor area for the ligand.
The high therapeutic activity of the afobazole is proved with anxious and anxiety and asthenic conditions corresponding to the experimental passive (stress-unstable) phenotype of an emotional and stress reaction.
Afobazol has a distinct anxiolytic property, which is not accompanied by a hypostatic effect (sedative effect is detected in Afobazole in doses, 40-50 times larger than ED50 for anxiolytic action). This is very important for working people who want to keep the usual activity. In addition, this feature contributes to high compliance. Aphobazol also affects a reduced mood and has moderately pronounced activating, vegetative stabilizing and anti-asthenic effects. The drug has no muscle relaxant properties, a negative impact on memory and attention indicators.
With its use, a drug dependence is not formed (which is important at long courses) and does not develop cancellation syndrome. This allows you to attribute this selective anxiolytic to the non-prescription.
In experiments on rats and cats, it has been established that afobazole in a dose of 5 mg / kg causes a more pronounced reinforcement of brain blood flow in rats that have undergone global transient ischemia compared with intact animals, which indicates the neuroprotective effect of the drug. There are also data on antimutagenic, stressboard and immunomodulating properties of Afobazole.
Therapy by this drug is practically not accompanied by side effects noted in 9% of patients. Those that are noted (light dizziness, headache, minor lethargy and nausea) are slightly pronounced; daily dose The drug or its cancellation and passed independently. In addition to good tolerability, Afobazole has a number of other advantages - low toxicity, favorable interaction profile with other drugs and is characterized by the simplicity of treatment regimen.

Literature
1. G.G. Loves, S.A. Sunyakov, D.V. Chumakov, L.E. Motemetov, "New Selective Anxiolytic Afobazol", Magazine of Neurology and Psychiatry named after S.S. Korsakov, 2005; 105: 4: 35-40
2. Senenin S. B., Badyshtov B.A., Lykovkov G.G. et al. Forecast of individual reactions to emotional stress and benzodiazepine tranquilizers, 2001.
3. Spelevich A.B., Drobyovyv M.Yu., Ivanov S.V. Clinical effects of benzodiazepine tranquilizers in psychiatry and general medicine, media sphere, Moscow, 2005.
4. Chumakov D.V. Peculiarities of Action of Anxiolytic Afobazole in Patients from Different Typological Groups // European Neurosschopharmacology, Moscow, S160, 2005.
5. KOLOTILINSKAYA N.V., Badyshtov B.A., Makhnycheva A.L. et al. Phase-i Investigation of Selective Anxiolytic Afobazole // EUROPEAN NEURPSYCHOWCHOrMacology, Moscow, S161, 2005.
6. Borodin V.I. The side effects of tranquilizers and their role in the border psychiatry // Psychiatrist. And psychopharmacol. - 2000. - № 3. - P. 72-74.;
7. Vane A.M. et al. Neurology for general practitioners. // Eidos Media, 2001.-504 s.;
8. Lawrence D. R., Benitt P. N. Side effects of medicinal substances // Clinical Pharmacology: in 2 tons / lane. from English - M.: Medicine, 1993. - T. 1 - pp. 254-294. - T. 2.- S. 54-80;
9. Hamilton M. Assessment of Anxiety Stages by Rating Br. J. MED PSYCHOL., 1959, 32. 50-55
10. A. B.Smulevich. Depression in general student practice. M., 2000.- 160 p.
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12. Beliles K, Stoudemire A. Psychopharmacologic Treatment of Depression In The MediCally Ill. Psychosomatics. 1998 May-jun; 39 (3): S2-19.
13. M.Yu. Crushing, psychopharmacotherapy in the general systematic network (somatotropic effects, compatibility with somatotropic drugs), Consilium Medicum, Volume 2 / No. 2/2000
14. Reference Cidale. Medicinal preparations in Russia. M., 2006.
15. Vertogradova O.P. Azapane / Medicinal preparations used in psychiatry. M., 1980, p.178-180
16. Mosolov S.N. Clinical application modern antidepressants. RMW. Psychiatry, 2005, Volume 13, №12, p.852-857

Anxiolyti (Tranquilizers) - a group of drugs that eliminate the alarm, anxiety that reduces mental tensions that cause muscle relaxation that stabilize the violation of vegetative functions.

In 1967, WHO introduced the term "anxiolyti", to determine the drugs, in Russia most often called tranquilizers (from lat. tranquillloare - Do calm, serene). The main drugs of this group are benzodiazepine derivatives. Tranquilizers of another chemical structure - hydroxyzine, Mebikar, Afobazol - Apply less frequently.

Classification of tranquilizers (anxiolytic drugs)

• 1. "Large" (strong) tranquilizers.
• 1.1. Benzodiazepine derivatives: bromdigidrochlorfenshbenzodiazepine ("Fenazepam"), diazepam ("Seduksen"), lorazepam ("Lorafen"), ocasazepam ("Nozepam").
• 1.2. Diffenylmethane derivatives: hydroxyzin ("Ataraks").
• 1.3. Tranquilizers of different chemical groups: tetramethylTeraazabicyclooktandion ("Mebikar"), afobazol, prophetus ("Program").
• 2. "Small" (daily) tranquilizers.
• 2.1. Benzodiazepine derivatives: medazepam ("Rudotel"), tofizopam ("Grandaxin"),
• 2.2. Other groups: buspiron ("Spetitown"), aminofenshaslaic acid ("Phoenibut")

The main property of tranquilizers is a decrease in mental activity without a violation of consciousness, physical, intellectual status - is associated with the suppression of a limbic brain system by increasing the actions of the brake mediator GABA.

In fig. 4.14 shows the scheme of the structure and functions of the benzodiazepine receptor, conjugate with the gaps to receptor and the chlorine channel.

Fig. 4.14.

BR - benzodiazepine receptor; Benzodiazepic molecule is depicted as a triangle; GAMK-R - GABA receptor; CL- - chloride passing through chlorine rope

The activation of the gamke-review of benzodiazepines leads to the discovery of the channel for chlorine and hyperpolarization of the postsynaptic membrane. In the absence of GAMK, benzodiazepines do not affect the conductivity of the chlorine neuronal membrane. However, not all the effects of benzodiazepines are mediated by the GAMK-benzodiazepine receptor complex. In large concentrations, benzodiazepines cause and amnesia, in the implementation of which other mechanisms can take part - inhibiting adenosine absorption, calcium permeability.

Intrapeceptor interactions are manifested in the activating (1) effect of gamc and benzodiazepine agonists on the chlorine channel, increasing the frequency of its openings. At the same time, the BSnzodiazepinovine agonists enhance (2) their own influence of the GAMK on the chlorine channel and increase the affinity of the GAMK-A-A-receptor to agonists (4), and the latter, in turn, increase the binding of benzodiazepines (5). Barbiturates are associated with a specific receptor (BR), in low doses increase (6) the time of finding the channel in the open state (after the activation of the GABA), and in high - directly open it (7). They also increase (8) the affinity of the GLMK receptor to agonists and contribute to the binding of the latter with a benzodiazepine receptor. The binding places of gamke and benzodiazepines on the GLMK receptor are presented in Fig. 4.15.

Fig. 4.15.

gray Mugs - Barbiturate Binding Places, Black Circle - Benzodiazepine Binding Plot

Specific benzodiazepine receptors were found in CNS cells. Benzodiazepine receptors are called the site (site) of benzodiazepine binding in the GAMK-A-receptor complex. Benzodiazepines, altohematically interacting with the GAMK-A receptor site, increase the affinity of gamma-amine oil acid to these receptors, while the flow of chlorine ions inside neurons due to the opening of ion channels. The brake postsynaptic potential increases, which reduces the excitability of neurons. The gamke-a-receptor complex is represented by five protein subunits - two α, two β and one γ. The schematic diagram of α1β2γ2 - the GAMK-A-receptor complex is presented in Fig. 4.16.

Each subunit has subtypes (α1_6, β1_3, γ1_3, etc.). GAMK-A-receptors, forming various combinations of subunits subtypes, have various properties, distribution in the brain, pharmacological and clinical effects.

Figure 4.16.

α1β2γ2 - protein subunits. In the center - chloride ion canal. Gaba Sue. - GAMK connecting the site at the boundary α1β2; BZD Site. Benzodiazepine binding a plot on the boundary α1γ2

The mechanism of the action of tranquilizers is associated with a decrease in their influence of the excitability of subcortical areas of the brain (limbic system, thalamus, hypothalamus) responsible for the implementation of emotional reactions, and the inhibition of interaction between these structures and the bark of the big brain. The emergence of emotions is usually associated with a limbic system, the basis of which is a circle of Paipets. Lymbic system - The complex of nerve structures of the final, intermediate and medium brain (belt and paragapocampal winding, hippocampus, hypothalamus, thalamus, almond-shaped body and other education) involved in the regulation of sleep, the state of wakefulness, concentration of attention, depth of emotions, in the formation of motivation of behavior. The limbic system is under the control of the frontal bark; It affects the work of all the cortical zones of the big brain. Almond-shaped body - The accumulation of the gray substance lying in the depths of the temporal share in front of the hippocampus in the immediate vicinity of the hook. This structure is part of a limbic brain system and controls motor and vegetative organism reactions associated with emotions. According to modern concepts, emotional arousal arises in the hippocampus, then goes into the hypothalamus and through the front core of the thalamus into the waist to the waist.

Tranquilizers reduce the excitability of subcortical areas of the brain and have an inhibitory effect on polysinaptic spinal reflexes, causing this muscle relaxation. Tranquilizers have an inhibitory effect on the progress of the excitation in the circle of Paipets, presented in Fig. 4.17.

Figure 4.17.

In contrast to neuroleptics, tranquilizers do not have a pronounced antipsychotic effect on delusional and hallucinatory disorders. They possess in varying degrees to four pharmacodynamic properties: anxiolytic, hypnotic, muscle relaxant and anticonvulsant.

Anxiolytic (antifobic ) and general focusing action - The most important feature of tranquilizers. Tranquilizers eliminate the feeling of fear, anxiety, voltage, anxiety. Therefore, they are used to treat various psychogenic disorders: neurasthenia, neurosis of obsessive states, hysteria, psychopathy. Due to the fact that fear, anxiety can manifest themselves with the expectation of surgical operation, serious stressful impacts, tranquilizers are applied not only in psychiatry.

Hypnotic effect It is expressed in facilitating sleep offensive, strengthening the action of sleeping pore; The effect of narcotic and painkillers is also intensified.

Mioryelaxantic effect Tranquilizers are associated with the effect on the CNS, and not with a peripheral strip-like action, so they are sometimes called central minelaxants. This effect is often a positive factor in the use of tensile tranquilizers, feelings of fear, excitation, however, it limits the use of drugs with a pronounced muscle relaxant property, in patients whose work requires a rapid, concentrated reaction (transport drivers, etc.).

Anticonvulsant action Allows you to use some tranquilizers (diazepams) to relieve convulsive syndrome.

When choosing a tranquilizer, it is necessary to take into account the differences in the spectrum of their action. Some preparations have all properties characteristic of tranquilizers (for example, diazepam) Others have anxiolytic action more pronounced. Some drugs (for example, mespam ("Rudotsel")) have a relatively weak muscle relaxant property, so they are more convenient for use in daytime and they are often called daily tranquilizers. However, in relatively large doses, all tranquilizers can show all pharmacological properties characteristic of this group.

Midazolam ("Dormicum") - a short-acting drug, half-life - 1-12 hours. With long-term use, it may cause symptoms of cancellation the next day in the form of anxiety enhancement. After his cancellation, insomnia can occur.

Flunitrzempam, clonazepam, Lorazepam ("Lorafen"), n itrazepam - Benzodiazepines medium duration Actions, have a half-life of 12-40 h. cause drowsiness in the first half of the day, if used as a sleeping pill.

Diazepam ("Seduksen"), chlordiazepoxide ("Elnyium"), bromdigidrochlorophenylbenzodiazepine ("Penazepam") - long-acting benzodiazepines with a half-life of 40-250 hours. When applying, there is a risk of accumulation in old age and in persons with severe liver function, but they cause the less pronounced "ricochet" effect and cancellation syndrome. The effect of "ricochet" occurs when the drug is terminated or decreases due to the fact that the drug is very quickly excreted from the body. It is manifested by the deterioration of the patient's condition due to the enhancement of the disease, to the elimination of which was directed by the drug.

Different tranquilizers are effective at various neurotic and neurotic states. Neurosis - These are face breakdowns, painfully experienced and accompanied by somatic vegetative and emotional-affective disorders. They do not have a causal bond with organic change in brain, as they relate to functional disorders. Features of neurosis:

• tendency to protracted flow;
• not accompanied by hallucinations and nonsense;
• Not accompanied by a decrease in the critical attitude of the patient to their disease.

The cause of neuroses: a combination of a psychogenic factor with certain circumstances, namely: a low or insufficient level of protection against a certain type of stress.

Anxolytic agents, or tranquilizers, improve person's adaptation to environmental conditions by eliminating emotional instability, reducing the sense of tension, anxiety, fear, anxiety.

Diazepam ("Seduksen", "Relium", "Valium") will stop all types of anxiety in neurosis, panic attacks, insomnia, obsessiveness with the presence of rituals, with the syndrome of the resident of De La Turnett (manifests itself in childhood and is characterized by multiple motor tics), normalizes the night sleep. Often it is appointed parenterally to treat persistent obsessions, can be used when the epileptic status is stopped.

Chlordiazepoxide ("Librium", "Elnyium") - historically the first of the benzodiazepine tranquilizers. It has a pronounced anti-leaving, anxiolytic and myarlaxing effect. Used in the treatment of obsessive states various character, neuroses, to relieve emotional stress, panic attacks.

Lorazepam ("Lorafen") has a powerful antifobic and sleeping pills, effectively applies with all types of neurosis for the treatment of hypochondriac, senthenetopathic disorders, contributes to the stabilization of the autonomic nervous system.

Hydroxyzin ("Ataraks") - a drug that is not addictive is used to treat asthenia, light phobic manifestations. The drug is a powerful vegue-corrector, shown to treat various somatizable disorders, relieves the feeling of heat tides, shortness of neurogenic origin, nausea, dizziness, sweating.

Tranquilizers have been widely used not only in psychiatric and neurological practice, but also in other areas of practical medicine.

The main areas of use of tranquilizers:

• Treatment of states accompanied by anxiety;
• Premedication - Preparations for operational intervention;
• Like sleeping pills;
• Removing seizures (using intravenous administration diazepama);
• Treatment of alcohol abstinence.

Side effects are associated with violation of the CNS activities: depression, drowsiness, violation of coordination of movements (ataxia), convulsions, violation of speech (dysarthria). Possible psychotic effects (paradoxical arousal, insomnia), other unwanted effects are marked by the gastrointestinal bodies - nausea, diarrhea, vomiting.

Perhaps addictive to benzodiazepines and the occurrence of drug addiction.

Persons performing work requiring a quick mental reaction and accurate coordination of movements (drivers of vehicles, pilots), most drugs are prescribed only under the condition of removing from work. Benzodiazepine derivatives that do not have a sleeping pills that do little affecting musculature tone ("day tranquilizers") - medazepam ("Rudotel"), tofizopam (Grandoxin), - less often cause drowsiness in daytime clock. Tranquilizers do not remove depression and are not applied to treat depressive states.

Despite the relatively small toxicity of the main tranquilizers (benzodiazepines, propaclene derivatives), they can be used only if there are appropriate indications and under medical supervision. Unreasonable and uncontrolled use can cause side effects, mental dependence and other unwanted effects. It should also be borne in mind that alcohol will potentiate the effect of tranquilizers, so during their use you can not use alcoholic beverages.

The name of the drug group Tranquilizers from the Latin language is translated as "soothing". Indeed, these drugs are able to calm down a person and eliminate such symptoms as anxiety, fear. That is why tranquilizers are prescribed with a neurotic spectrum disorders.

Pharmacological groups of tranquilizers

Tranquilizers (synonym for anxiolitics) exist more than sixty years. The first representatives of this group are meepobamat, chloridiazepoxide and diazepams. Now the group of tranquilizers has about a hundred drugs.

Tranquilizing properties have various drugs in the chemical structure. Depending on the origin, the following groups of tranquilizers distinguish:

1. Benzodiazepine derivatives (diazepams, phenazepams, oxazepam, chloridiazepoxide);
2. Diphenylmethane derivatives (hydroxyzine (atarax), biennock);
3. Carbamates (Meproamat);
4. Different (trioxazine, adaptol, afobazole).

The most frequently used group of tranquilizers is benzodiazepines. They have the most pronounced tranquilizing effect. However, the incorrect use of benzodiazepines can lead to the formation of addiction and dependence. Modern medications Such as an atarae, Afobazol do not have such side effects, but at the same time have a less pronounced tranquilizing effect.

Indications for the use of tranquilizers

How do tranquilizers work? Preparations of various groups have an unequal mechanism of action. Thus, benzodiazepines activate GAB-receptors through special benzodiazepine receptors located in the central nervous system. This leads to increased receptor susceptibility to the gamke - neuromediator, which has a braking effect on the nervous system. Such a pharmacological impact leads to the fact that a person calms down, relaxes.

Tranquilizers reduce the excitability of subcortical CNS structures responsible for the emotional reaction of a person, as well as slow down the interaction between the specified structures and the brain bark.

Tranquilizers have several pharmacological effects:

• Tranquilizing (Anxiolytic) - manifests itself in the form of elimination of alarm, fear, anxiety, internal stress.
• Sedative - It is expressed in reducing psychomotor excitation, reducing the concentration of attention, the rate of mental, motor reactions.
• Miorlaxantic - manifests itself by eliminating muscle tension.
• Anti-slip - It is expressed in reducing convulsive activity.
• Hypnotic - It is expressed in the acceleration of sleep offensive, improving its qualities.

These effects in various drugs are expressed in an unequal degree, which should be considered when choosing a medicine. So, for example, a sedative effect is very pronounced by diazepam, a phenazepama and mespama is weak. And the anticonvulsant effect is maximally expressed in diazepama, clonazepama.

Some tranquilizers have a vegetable stabilizing effect, that is, normalize the activities of the autonomic nervous system. This is manifested by a decrease arterial pressure, heartbeat, eliminating excessive sweatiness.

Note!Tranquilizers have a potentiary effect. Their use enhances the influence of sleeping pills, painkillers, anesthesia. That is why tranquilizers often introduce patients to surgical operations.

Tranquilizers practically do not eliminate psychotic disorders (hallucinations, nonsense), therefore do not apply in the treatment of endogenous mental diseases :, bar. The exclusion is metal-based psychosis, which are successfully born with taking tranquilizers.

Thus, the testimony for the use of anxiolytics are:

1. (accompanied by anxiety, fear, motor anxiety);
2. Alarming disorders;
3. Panic disorder;
4. Obsessive compulsive disorder;
5. with alcoholism, metal-nutty psychosis;
6. Hypercines, ticks;
7. Premedication (preparation for surgical intervention).

It is worth noting that the range of use of anxiolyts has long been beyond the treatment of mental diseases. Thus, these drugs are prescribed under psychosomatic diseases:, ulcerative disease, as well as with dermatological diseases accompanied by itching.

Features of application

The decision on the need for treatment with tranquilizers only receives a doctor. The use of this group of drugs requires compliance special conditions. First of all, it is necessary to take into account the fact that the use of most tranquilizers, especially benzodiazepines, may result in addiction. To avoid this dose of the tranquilizer, increase gradually, reaching optimal. The duration of use should not exceed two or three weeks. At the end of the course of treatment, the drug dose is reduced gradually. If you need long-term treatment, the tranquilizer is prescribed by courses with interruptions between them.

Note! Modern anxiolists of nonsense do not cause addiction, so it can be applied longer. The duration of treatment is determined by the doctor.

Tranquilizers, as already mentioned, have a sedatory impact on a person, which can manifest itself in a deterioration in the concentration of attention. Therefore, in the treatment of tranquilizers, you should not drive a car. The least expressed seding effect in the "daytime" tranquilizers - guidazepama, trifimosine, Mebikar, Atarax.

Important! The joint use of anxiolytic and alcohol is contraindicated, as this leads to a pronounced oppression of the nervous system.

Side Effects, Contraindications

Possible side effects in the treatment of tranquilizers are mainly associated with the oppression of the nervous system. This is manifested in the form of daylight, lethargy, the sensation of "breakdown", dull emotional reactions ,. It is also possible to appear such side effects as muscle weakness, arterial hypotension, dryness in the mouth, dyspeptic phenomena, potency disorders.

The use of benzodiazepine tranquilizers can lead to the formation of addiction, drug dependences manifested in the form of cancellation syndrome. This syndrome is manifested after a sharp cancellation of the medication in the form of insomnia, fear, irritability, tremor, seizures, and sometimes even depersonalization, hallucinations. The risk of drug addiction increases with long-term therapy with tranquilizers.

Contraindications for the purpose of tranquilizers:

1. Pregnancy, lactation period;
2. Miasti;
3. Liver failure;
4. Respiratory failure;
5. Alcoholic, (except for the relief of the abstinence syndrome);
6. (for benzodiazepine tranquilizers).

Benzodiazepine tranquilizers are not prescribed to persons under the age of eighteen. Only in cases of extreme necessity, their appointment can be justified in this age group.

Popular tranquilizers

Important! Benzodiazepine tranquilizers are prescription preparationswho are released in a pharmacy for the appointment of a doctor. Anxiolytic other origin is sold without recipeTherefore, they are greater popular among patients. But it is worth emphasizing , that self-treatment with psychotropic drugs is unacceptable.

One of the oldest tranquilizers belongs to the group of benzodiazepines. Also known under such names as "Sibazon", "Relanium", "Sedukesen", "Valium". Produced in the form of tablets and solution for injections. The sedent effect appears several minutes after intravenous and half an hour after intramuscular administration.

The medicine effectively eliminates the alarm, fear, normalizes night's sleep. Therefore, diazepams are prescribed for neurosis, panic and osne-compulsive disorders, with turret syndrome, as well as to relieve abstineet syndrome.

In addition, diazepam has pronounced anticonvulsant and muscle relaxing effects. Therefore, it is often prescribed to eliminate convulsive seizures. Diazepams are used for premium before carrying out endoscopy and operations.

Guidazepam

Refers to the group of benzodiazepines, however, unlike other representatives of this group, it has an activating effect, and hypnotic and mineral effects are weakly expressed.

Gydazepams refer to "daytime" tranquilizers. Its anxiolytic effect is manifested by a decrease in the feeling of anxiety, fear and anxiety. The drug is prescribed for the treatment of neurosis, psychopathy, vegetative lability, logo-formation (stuttering), abstinence alcohol syndrome.

Ataraks.

Active ingredient - hydroxyzine, piperazine derivative. Atarax is a nebenzodiazepine anxiolytic, refers to the group H1-histamine blockers. The drug is counted for "soft" tranquilizers, it has a moderate anxiolytic effect. Tablets are available in the form of tablets, sedative action is developing fifteen-thirty minutes later.

The main indications of its use are anxiety, increased excitability, dermatological diseases accompanied by itching, alcohol abstineent syndrome. In addition to sedative and anxiolytic, there is also a controversial action. Unlike benzodiazepines, Ataras does not cause addiction and dependence.

Afobazol.

Not sensiatediazpine anxiolytic, produced in the form of tablets. The active substance is Fabothizol. It has moderate anxiolytic and activating actions.

Indications for use: neurasthenia, anxiety disorder, abstineent syndrome, adaptation disorders, psychosomatic diseases. A tangible effect develops on the fifth-seventh days of treatment, and maximum effect Four weeks later.

The effect of the drug is very mild and less pronounced than the action of benzodiazepines. However, the advantage of Afobazole is that its application does not lead to addiction and dependence.

G. Valeria, Medical Observer

Natural anxiolyti There may be a great ally when nervousness and anxiety increase. Their effectiveness allows people to calm themselves, reduce their state of activity.

Currently, there are various measures to achieve these goals. However, studies show that the most widely selected option around the world is the use of natural anxiolytic.

In fact, the data of the Ministry of Health on the consumption of drugs with anxolytic properties show that more than 11% of the population as a whole use them.

These medicines are useful and even needed in many cases. However, they also concern a number of risks and negative consequences.

For this reason, anxiolytic drugs are not always the best option, so it is often convenient to look for alternatives.

In this sense, alternative medicine gained strength over the past few years. An increasing number of studies analyze the effectiveness of various natural anxiolitics.

Moreover, natural anxiolitics are very useful solutions for a large number of cases. It is usually argued that antexolitics of natural origin is particularly effective in the treatment of soft disturbing disorders, stressful states and situations of transitional nervous activity.

The best natural anxiolitics

Now we comment on the 12 natural anxiolyts that have shown more efficiency and are currently used as tranquilization elements.

Valerian

Valerian is a perennial plant belonging to the Valerianide family. It is found both in Europe and in Asia and North America and is one of the main plants used for anxiolytic purposes.

The widespread use of Valerians currently as an anxiolytic element is justified by its efficiency. In fact, his soothing effect was opposed in several studies.

Thus, Valerian is one of natural anxiolytics with the greatest proof of its effectiveness. In particular, this is a very good option to achieve the state of relaxation and to stimulate sleep in people suffering from insomnia.

Valerian sedative effects are associated with their essential oils, as they are associated with GAB-receptors and allow inhibiting the reverse grip of neurotransmitters.

Studies show that their consumption causes a moderate sedative effect on the central nervous system. Similarly, it was shown that it is effective in the treatment of generalized nervousness, anxiety, insomnia, state of concern and tension.

Other studies analyzed its impact on the treatment of heavier alarming disorders. However, in these cases, the final results are not received.

Finally, it was shown that Valerian has antispasmodic activity in smooth muscles, so it is also given in cases of gastrointestinal pains of nervous origin.

California Mak.

Eschoscholzia Californica, widely known as "Poppi California", is a type of papavacium belonging to the subfamily of Eschascholzioidea, native California.

It stands out with his appearance and is used as decorative, since in the summer it offers numerous bright orange flowers. In addition, its consumption produces relaxing effects.

In particular, California poppy has sleeping bags-relaxing elements, so it is very effective for fighting insomnia in children and the elderly.

Its consumption causes a soft and resistant sedative effect on the central nervous system. And it is also used to reduce easy anxiety, control over-neuropiness and combating irritability and stressful states.

Brain effects arise on a neurotransmitter GABA, dopamine and monoamines. Nevertheless, the study of this plant is somewhat meager.

In fact, there is one controlled study that studied its consequences. The results showed that the Californian poppy made a slight decrease in the symptoms of anxiety.

Finally, it is also used to calm the stroke, alleviate migraine and muscle seizures, and is considered good support to reduce hypertension.

Tila

Tila is another of the substances that are used in the most popular forms to combat nervousness states. It consists of infusion, which is produced by the fruit of some species of the genus Tilla.

Tila is allocated by its antispasmodic, dubious and anxolytic properties, since in its composition it has alpha-pinen, citric, nerve and seine acid.

This natural anxiolytic helps to relax the nervous tension and acts as relaxing muscles, so it performs a generalized anxiolytic effect.

In addition, its effects act not only on the central nervous system, but also affect the liver. In particular, Tila is responsible for increasing its detoxification function, the aspect required for muscle and nervous relaxation.

Studies of its effectiveness have shown that Tila is a suitable element for interference in anxiety, anxiety and excitement.

Paciflower

Passionflower is one of the birth of the Passiflaraceae family, plants common in tropical America, Asia, Australia and Oceania.

It is widely known as a passion flower, and its consumption produces a wide relaxing effect of natural anxiolytic.

Anxolytic potential of passiflores is high, to such an extent that some studies compare it with the effects of valium.

In general, this plant is useful to reduce anxiety, increasing calm and interference in insomnia, heartbeat and nervous disorders.

His moderate activity makes it a natural anxiolytic, especially useful for children. Nevertheless, it is contraindicated for children less than two years and pregnant or nursing women.

Chamomile

Roman chamomile or ordinary chamomile is a perennial plant of the AsteracEae family. It is mainly found in Europe and is consumed mainly by infusions.

Its anxiolytic effect corresponds to the active chamomile component, flavoid, known as Apigenin.

This substance performs moderate tranquillative actions, ensures sleep.

Hop

Humulus Lupulus, more famous as hops, is one of the three types of Humulu genus, the Cannabis family. And he is widely known for its involvement in brewing.

This plant also has soothing elements. In particular, its use is indicated for the treatment of nervous disorders associated with menopause. However, due to its incidence in estrogen, it is important to consult with the doctor before using hops as a natural anxiolytic agent.

Hop produces a hypnotic sedative effect of the nervous system, therefore it is also effective in the treatment of hyperoportability, anxiety and insomnia.

Yellow calderon

Yellow calderon is a perennial and strong plant, which for centuries was used in traditional Chinese medicine.

This is explained by anti-aging and aphrodisiac properties and contains antioxidant alkaloids. In addition, recent studies have shown that its consumption also provides tranquilization effects.

In particular, recent clinical study It showed that a water-alcohol extract with a content of 50.3 mg / g Galfimine B had an anxiolytic effect, superior to the lorazepam.

In addition, in the study, the yellow extract of Calderon turned out to be well tolerated subjects and without side effects.

Thus, although further research requires, this plant demonstrates promising results and may be a powerful natural anxiolytic.

Asian Centella

Asian CENTELLA is a small annual herbaceous plant of the Apicae family. It is found mainly in Asia, as well as known as Cola, Antanan and Pegagi.

This plant is often used as medicinal grass In Ayurvedic medicine and in traditional Chinese medicine. It is usually consumed in a salad or similar nutritional preparations.

The main properties attributed to it include: Cycatatrians, anti-rich agents, psycho-cells, contraceptives, antioxidants, anti-inflammatory, and angiogenic, antiprofilative, antimicrobial and antimutagenic.

Thanks to its extensive properties, the European Medicine Agency (EMEA) has notified about several drugs. Basically, it is used in treating:

• syphilis
• hepatitis
• dysentery
• anemia
• asthma
• bronchitis
• cellulite
• constipation
• urethritis
• epilepsy
• hypertension
• Peripheral cirrhosis
• Toothache

Similarly, it is also explained by the sedative properties. The study of its soothing effects has shown its effectiveness in the fight against anxiety, however, it was studied only in mice.

Chirimia

Cherimoya - edible fruit of Annona Cherimola tree, plants belonging to the Annonaceae family.

It is food rich in potassium and vitamin C, and its consumption contributes to a large amount of carbohydrates, among which glucose and fructose prevail.

Its consumption contributes to the absorption of iron from food, resistance to infections and performs an important antioxidant function.

In Pain medicinal application This natural anxiolytic is used to treat anemia, arthritis, cholesterol, stomach reductions, growth, body weakness, organic weakness, diabetes, dyspepsia, spasm of stomach, hypertension, cardiovascular problems, osteoporosis, rheumatism and intestinal regulation.

In addition, clinical trials in rodents have shown that the various active principles of Cherimoya are associated with the brain gamiergic systems, and they are generating soothing effects.

Cannes

Cannes - a plant born in South Africa, possessing interesting pharmacological properties and insignificant side effects.

It is accepted inside, intranasally and sublingual and consists of inhibitors of the alkaloids of the inverse seizure of serotonin, the cause of which represents a high psychopharmacological potential.

Inhibition, which leads to the consumption of this substance when taking serotonin, motivates an increase in this substance in the brain.

Thus, Cannes acts similarly to many psychotropic drugs and is a very promising natural anxiolytic for the treatment of mood, anxiety, nervousness and stress disorders.