Nootropics

Nootropics (neurometabolic stimulants, cerebroprotectors) are psychoanaleptic drugs that can activate neuro-metabolic processes in the brain and have an antihypoxic effect also increase the overall resistance of the organism to the action of extreme factors. Many other drugs also have neuro-metabolic and cerebroprotective effects, including angioprotectors, adaptogenic cholinergic drugs, vitamins, antioxidants, amino acids, anabolic steroids, certain hormones (especially synthetic tiroliberins), thiol antidotes, etc.

[1], [2], [3]

Indications for the use of nootropics

Diseases of the central nervous system, accompanied by a decrease in intelligence and memory impairment; dizziness, decreased concentration, emotional lability; treatment of stroke; dementia due to impaired cerebral circulation, Alzheimer's disease; comatose state of vascular, traumatic or toxic origin; depressive conditions; psycho-organic syndrome (asthenic variant); relief of withdrawal syndrome and delirious conditions in alcoholism, drug addiction; neurotic states with predominance of asthenia; disability learning in children, not related to socio-educational neglect (as part of combination therapy): sickle cell anemia (as part of combination therapy); cortical myoclonus.

In psychiatric practice, appoint a course of treatment (1-3 months) or short intermittent courses for 3-5 days at intervals of 2-3 days for 1-3 months for several courses per year.

Mechanism of action and pharmacological effects of nootropics

Nootropics are medicines that exert a direct activating influence on the integrative mechanisms of the brain, stimulate learning, improve memory and mental activity, increase brain resistance to "aggressive" effects, improve cortico-subcortical connections. The term "nootropism" was first proposed by C. Giurgeal (1972) to characterize the specific properties of 2-oxo-1-pyrrolidinyladamide as a psychoanaleptic that activates integrative processes in the brain that facilitates interhemispheric and cortical-subcortical interactions, which increases the resistance of the brain to amnesic effects.

Currently, this group of drugs includes more than three dozen names. In the clinical practice, pyrrolidine derivatives (piracetam), meclofenoxate and its analogues (meclofenoxate), pyrithinol (pyriditol, encephabol) were introduced. To nootropics also include preparations of GABA and its derivatives (aminalon, sodium hydroxybutyrate, aminophenylbutyric acid (phenybut), hapanthenic acid (pantogam), nicotinoyl-gamma-aminobutyric acid (picamylone), some herbal remedies, in particular preparations from Ginkgo biloba (tanakan, oxyvene).

By pharmacological properties nootropics differ from other psychotropic drugs. They do not significantly affect the spontaneous bioelectric activity of the brain and motor reactions, do not have hypnotic and analgesic effects and do not change the effectiveness of analgesics and hypnotic drugs. However, they have a characteristic effect on a number of functions of the central nervous system, facilitate the transfer of information between the hemispheres, the brain, stimulate the transmission of excitation in the central neurons, improve the blood supply and energy processes of the brain, increase its resistance to hypoxia.

Since nootropic drugs are created on the basis of substances of biogenic origin and act on metabolic processes, they are considered as a means of metabolic therapy - the so-called neurometabolic cerebroprotectors. The main biochemical and cellular effects of nootropics on the brain are the activation of metabolic processes, including increased utilization of glucose and the formation of adenosine triphosphate, stimulation of protein and RNA synthesis, inhibition of lipoxidation, stabilization of plasma membranes. The general neurophysiological correlate of the pharmacological action of nootropics is their facilitating effect on glutamatergic transmission, enhancement and lengthening of long-term potentiation - LTP. These effects are typical for the influence on the central nervous system of various mnemotropic nootropics such as pyracetam, phenylpyrazetam (phenotropil), idebenone, vinpocetine, mexidol. It is suggested that the age-related decrease in the density of NMDA receptors in certain areas of the cortex and the hippocampus is the reason for the weakening of cognitive functions of the brain during aging. These representations predetermine the pharmacological application of substances stimulating glutamatergic neurotransmission by means of agonists of glycine sites or glutamate receptor-increasing compounds as nootropics.

Participation in the neurophysiological mechanisms necessary for the realization of the learning and memory processes, dopamine, cholino and andrensic structures of the brain was established. According to some authors, corticosteroids play an important role in the manifestation of myotropic effects of nootropics. Indeed, high doses of corticosteroids inhibit the positive effects of nootropics on memory and learning; It is also established that in most patients with Alzheimer's disease the level of steroid hormones is increased. It should be noted that the neurophysiological and molecular bases of learning and memory processes remain insufficiently deciphered by biological phenomena. At the same time, the medicinal preparations of various pharmacological groups - actually nootropics, psychostimulants, adaptogens, antioxidants, etc., have a positive effect on the memory disturbances observed with a whole series of actually psychic and somatic disorders. The improvement of mnestic functions is observed in experimental and clinical conditions with the use of pharmacological agents , acting on various sides of the brain metabolism, the level of free radicals, the exchange of neurotransmitters and modulators.

Clinically, neurometabolic stimulants have psychostimulating, anti-asthenic, sedative, apoptosis, antiepileptic, actually nootropic, mnemotropic, adaptogenic, vasovetagative, antiparkinsonian, aitidiskinetic effect, increase wakefulness level, clarity of consciousness. Regardless of the register of mental disorders, their main action is directed to acute and residual organic insufficiency of the central nervous system. The selective therapeutic effect they have on cognitive disorders. Some neurometabolic stimulants (phenibut, picamilon, pantogam, mexidol) have sedative or tranquilizing properties; in most drugs (acephene, bemitil, pyrithinol, pyracetam, aminalon, demanol), psychostimulating activity is noted. Cerebrolysin has neuron-specific neurotropic activity similar to that of natural factors of neuronal growth, improves the efficiency of aerobic energy metabolism of the brain, improves intracellular protein synthesis in the developing and aging brain.

Characteristics of individual groups of drugs

Phenylpyrazetam (N-carbamoyl-methyl-4-phenyl-2-pyrrolidone) is a domestic drug that, according to its basic pharmacological action, belongs to the nootropic drug, was registered and approved for industrial production by the Russian Ministry of Health in 2003. Phenylpyra- cetam, like pyracetam, to pyrrolidone derivatives, i.e. Its basis is closed in the cycle of GABA - the most important brake mediator and regulator of the action of other mediators. Thus, phenylpyraketam, like most other nootropics, is close in chemical structure to endogenous mediators. However, unlike pyracetam, phenylpyracetam has a phenyl radical, which determines a significant difference in the spectra of pharmacological activity of these preparations.

Phenylpyra- cetam is rapidly absorbed from the digestive tract and easily * passes through the blood-brain barrier. Bioavailability of the drug with oral intake is 100%, the maximum concentration in the blood is reached in an hour. Phenylpyricetam is completely eliminated from the body within 3 days, the clearance is 6.2 ml / (minxkg). Elimination of phenylpyricetam is slower than pyracetam: T1 / 2 is 3-5 and 1.8 hours, respectively. Phenylpyracetam is not metabolized in the body and is excreted unchanged: 40% is excreted in the urine and 60% - with bile and sweat.

Experimental and clinical studies have established that phenylpyracetam has a wide spectrum of pharmacological effects and for a number of parameters favorably differs from piracetam. Indications for the use of phenylpyricetam:

• chronic cerebrovascular insufficiency;
• ITC;
• asthenic and neurotic states;
• violation of learning processes (improves cognitive functions);
• depression of mild and moderate severity;
• psycho-organic syndrome;
• convulsive conditions;
• chronic alcoholism; :
• obesity of alimentary-constitutional genesis.

Phenylpyricetam can also be used by healthy people to reinforce mental and physical activity, increase resistance and level of life in extreme conditions (stress, hypoxia, intoxication, sleep disturbance, trauma, physical and mental overload, fatigue, cooling, immobility, pain syndromes).

The significant advantage of phenylpyra- cetamine in front of pyracetam is indicated by the rates of the onset of the effect and the values of the active doses, revealed both in the experiment and in the clinic. Phenylpyra- cetam does not work without a single injection, and the course of its use ranges from 2 weeks to 2 months, whereas the effect of pyracetam occurs only after a course of treatment lasting 2-6 months. The daily dose of phenylpyrazetam is 0.1-0.3 g, (and piracetam - 1.2-12 g, another undeniable advantage of the new drug is that when it is used there is no addiction, dependence, withdrawal syndrome.

[6], [7]

Contraindications to the use of nootropics

Individual hypersensitivity, psychomotor agitation, hepatic and renal insufficiency, bulimia.

When using drugs with stimulating activity in the elderly, transient phenomena of hyperstimulation are possible in the form of anxiety, liveness, and sleep disturbances.

[4], [5]

Side effects

Side effects are most often observed in elderly patients in the form of increased irritability, excitability, sleep disturbances, dyspeptic disorders, as well as frequent episodes of angina pectoris, dizziness, tremor. Less common are weakness, drowsiness, convulsions, motor disinhibition.

Toxicity

The LD50 value of phenylpyricetam is 800 mg / kg. Comparing the doses in which the drug exhibits nootropic properties (25-100 mg / kg), with its LD50, it can be concluded that it has a sufficiently wide therapeutic range and low toxicity. The therapeutic index, calculated as the ratio of the therapeutic and toxic dose, is 32 units.

Clinical trials conducted at the State Scientific Center for Social and Forensic Psychiatry. V.P. Serbian, Moscow Research Institute of Psychiatry, the Russian Center for Autonomic Pathology and other authoritative centers, have confirmed the high effectiveness of this drug.

Thus, phenylpyracetam is a nootropic new generation with a unique spectrum of neuropsychotropic effects and mechanisms of action. The use of phenylpyricetam in medical practice can significantly improve the effectiveness of treatment and put the quality of life of patients with CNS pathology to a new level.

Noopept - a new domestic drug with nootropic and neuroprotective properties. By chemical structure, this is ethyl ester of N-phenyl-acetyl-b-prolyl-glycine. When ingestion, the noopept is absorbed in the digestive tract and enters the systemic blood stream unchanged; the relative bioavailability of the drug is 99.7%. AT ; the body produces six metabolites of noopept - three phenyl-containing and three desphenyl. The main active metabolite is cycloprolylglycine, identical to the endogenous cyclic dipeptide with nootropic activity.

The study of the chronic toxicity of the preparation in experimental animals at doses exceeding the average nootropic dose from 2 to 20 times showed that noopept does not have a damaging effect on internal organs, does not lead to significant disturbances in behavioral reactions, changes in hematological and biochemical indices. The drug does not have an immunotoxic, teratogenic effect, does not show mutagenic properties, does not adversely affect the postnatal development of the offspring and the generative function. The maximum expressed antiamnestic effect is defined in doses of 0.5-0.8 mg / kg. The duration of action is 4-6 hours after a single injection. With an increase to 1.2 mg / kg, the effect disappears ("dome-shaped" dependence).

Nootropic effect of noopept is selective. The drug in a wide range of doses (0.1-200 mg / kg) does not show any stimulating or sedative effect, does not disrupt the coordination of movements, does not cause muscle relaxant action. Prolonged use of noopept in a dose of 10 mg / kg does not lead to a change in the spectrum of its neurotropic activity, there is no cumulative effect, the development of tolerance and the emergence of new components of the drug. When the drug is withdrawn, minor activation phenomena are established, without signs of development of the "ricochet" anxiety characteristic of some nootropics. For clinical use, the recommended dose of noopept is 20 mg / day.

The presence of a broad spectrum of nootropic and neuroprotective activity in noopept was established in patients with impaired memory, attention and other intellectual-mnestic functions after CCT and with chronic cepebo-vascular insufficiency. When taking noopept compared with pyracetam, the incidence of side effects of therapy decreases (12% and 62%, respectively). The effectiveness and good tolerability of noopept allows us to recommend it as a drug of choice in the therapy of neurotic disorders.