Nootropics

Nootropics (neurometabolic stimulants, cerebroprotectors) are psychoanaleptic drugs that can activate neurometabolic processes in the brain and have an antihypoxic effect, as well as increase the overall resistance of the body to extreme factors. Many other drugs also have neurometabolic and cerebroprotective effects, including angioprotectors, adaptogens, cholinergic drugs, vitamins, antioxidants, amino acids, anabolic steroids, some hormones (especially synthetic thyroliberins), thiol antidotes, etc.

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Indications for the use of nootropics

CNS diseases accompanied by decreased intelligence and memory impairment; dizziness, decreased concentration, emotional lability; stroke treatment; dementia due to cerebrovascular accident, Alzheimer's disease; comatose states of vascular, traumatic or toxic genesis; depressive states; psychoorganic syndrome (asthenic variant); relief of withdrawal syndrome and delirious states in alcoholism, drug addiction; neurotic states with a predominance of asthenia; learning disabilities in children not associated with social and pedagogical neglect (as part of combination therapy): sickle cell anemia (as part of combination therapy); cortical myoclonus.

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

Mechanism of action and pharmacological effects of nootropics

Nootropics are drugs that have a direct activating effect on the integrative mechanisms of the brain, stimulating learning, improving memory and mental activity, increasing the brain's resistance to "aggressive" effects, and improving cortico-subcortical connections. The term "nootropic" was first proposed by C. Giurgeal (1972) to characterize the specific properties of 2-oxo-1-pyrrolidinyl adetoamide as a psychoanaleptic that activates integrative processes in the brain, facilitates interhemispheric and cortical-subcortical interactions, and increases the brain's resistance to amnestic effects.

Currently, this group of drugs includes more than three dozen names. Pyrrolidine derivatives (piracetam), meclofenoxate and its analogues (meclofenoxate), pyritinol (pyriditol, encephabol) have been introduced into clinical practice. Nootropics also include GABA drugs and its derivatives (aminalon, sodium oxybutyrate, aminophenylbutyric acid (phenibut), hapantenic acid (pantogam), nicotinoyl-gamma-aminobutyric acid (picamilon), some herbal remedies, in particular drugs from Ginkgo biloba (tanakan, oxyvel).

In terms of pharmacological properties, nootropics differ from other psychotropic drugs. They do not significantly affect the spontaneous bioelectrical activity of the brain and motor reactions, do not have a hypnotic or analgesic effect, and do not change the effectiveness of analgesics and hypnotics. At the same time, they have a characteristic effect on a number of CNS functions, facilitate the transfer of information between the hemispheres of the brain, stimulate the transfer of excitation in the central neurons, improve blood supply and energy processes in the brain, and increase its resistance to hypoxia.

Since nootropic drugs are created on the basis of substances of biogenic origin and affect metabolic processes, they are considered as 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 glucose utilization 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, strengthening and prolongation of long-term potentiation - LTP. These effects are characteristic of the influence on the central nervous system of such various mnemotropic nootropics as piracetam, phenylpiracetam (phenotropil), idebenone, vinpocetine, mexidol. It is suggested that age-related decrease in NMDA receptor density in certain areas of the cortex and hippocampus is the cause of weakening of cognitive functions of the brain with aging. These ideas predetermine the pharmacological use of substances stimulating glutamatergic neurotransmission using glycine site agonists or compounds that increase glutamate receptor density as nootropics.

It has been established that dopamine, cholinergic and andrenergic structures of the brain participate in neurophysiological mechanisms necessary for the implementation of learning and memory processes. According to some authors, corticosteroids play a significant role in the manifestation of mnemotropic effects of nootropics. Indeed, high doses of corticosteroids suppress the positive effect of nootropics on memory and the learning process; it has also been established that the level of steroid hormones is elevated in most patients with Alzheimer's disease. It should be noted that the neurophysiological and molecular bases of learning and memory processes remain insufficiently deciphered biological phenomena. At the same time, drugs of various pharmacological groups - nootropics, psychostimulants, adaptogens, antioxidants, etc. - have a positive effect on memory impairment observed in a number of mental and somatic disorders. Improvement of mnemonic functions is observed in experimental and clinical conditions when using pharmacological agents that affect various aspects of brain metabolism, the level of free radicals, the exchange of neurotransmitters and modulators.

Clinically, neurometabolic stimulants have a psychostimulating, antiasthenic, sedative, antidepressant, antiepileptic, nootropic, mnemotropic, adaptogenic, vasovegetative, antiparkinsonian, antidyskinetic effect, increase the level of wakefulness, clarity of consciousness. Regardless of the register of mental disorder, their main effect is addressed to acute and residual organic insufficiency of the central nervous system. They have a selective therapeutic effect on cognitive disorders. Some neurometabolic stimulants (phenibut, picamilon, pantogam, mexidol) have sedative or tranquilizing properties, most drugs (acefen, bemitil, pyritinol, piracetam, aminalon, demanol) have psychostimulating activity. Cerebrolysin has neuron-specific neurotropic activity similar to the action of natural neuronal growth factors, increases 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

Phenylpiracetam (N-carbamoyl-methyl-4-phenyl-2-pyrrolidone) is a domestic drug, which by its main pharmacological action is related to a nootropic drug, registered and approved for industrial production by the Ministry of Health of Russia in 2003. Phenylpiracetam, like piracetam, is a derivative of pyrrolidone, i.e. its basis is a closed GABA cycle - the most important inhibitory mediator and regulator of the action of other mediators. Thus, phenylpiracetam, like most other nootropics, is close in chemical structure to endogenous mediators. However, unlike piracetam, phenylpiracetam has a phenyl radical, which determines a significant difference in the spectra of pharmacological activity of these drugs.

Phenylpiracetam is rapidly absorbed from the gastrointestinal tract and easily *8 passes the blood-brain barrier. The bioavailability of the drug when taken orally is 100%, the maximum concentration in the blood is achieved in an hour. Phenylpiracetam is completely eliminated from the body within 3 days, the clearance is 6.2 ml / (min x kg). The elimination of phenylpiracetam is slower than piracetam: T1 / 2 is 3-5 and 1.8 hours, respectively. Phenylpiracetam 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 phenylpiracetam has a wide range of pharmacological effects and compares favorably with piracetam in a number of parameters. Indications for the use of phenylpiracetam:

• chronic cerebrovascular insufficiency;
• TBI;
• asthenic and neurotic conditions;
• learning disabilities (improves cognitive functions);
• mild to moderate depression;
• psychoorganic syndrome;
• convulsive states;
• chronic alcoholism;:
• obesity of alimentary-constitutional genesis.

Phenylpiracetam can also be used by healthy people to enhance mental and physical activity, increase resistance and vitality levels under extreme conditions (stress, hypoxia, intoxication, sleep disturbances, injuries, physical and mental overload, fatigue, hypothermia, immobility, pain syndromes).

The significant advantage of phenylpiracetam over piracetam is demonstrated by the speed of onset of the effect and the size of the effective doses, revealed both in the experiment and in the clinic. Phenylpiracetam acts already after a single administration, and the course of its use is from 2 weeks to 2 months, while the effect of piracetam occurs only after a course of treatment lasting 2-6 months. The daily dose of phenylpiracetam is 0.1-0.3 g, (and piracetam - 1.2-12 g; another undeniable advantage of the new drug is that its use does not cause addiction, dependence, or withdrawal syndrome.

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Contraindications to the use of nootropics

Individual hypersensitivity, psychomotor agitation, liver and kidney failure, bulimia.

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

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Side effects

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

Toxicity

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

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

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

Noopept is a new domestic drug with nootropic and neuroprotective properties. Chemically, it is ethyl ester of N-phenyl-acetyl-b-prolyl-glycine. When taken orally, noopept is absorbed in the digestive tract and enters the systemic bloodstream unchanged; the relative bioavailability of the drug is 99.7%. Six metabolites of noopept are formed in the body - three phenyl-containing and three desphenyl. The main active metabolite is cycloprolylglycine, identical to the endogenous cyclic dipeptide with nootropic activity.

A study of the chronic toxicity of the drug in experimental animals at doses exceeding the average nootropic dose by 2 to 20 times showed that noopept does not have a damaging effect on internal organs, does not lead to significant disruptions in behavioral reactions, or changes in hematological and biochemical parameters. The drug does not have an immunotoxic, teratogenic effect, does not exhibit mutagenic properties, and does not adversely affect the postnatal development of offspring or the generative function. The most pronounced antiamnestic effect is determined at doses of 0.5-0.8 mg/kg. The duration of action is 4-6 hours after a single administration. When it is increased to 1.2 mg/kg, the effect disappears (“dome-shaped” dependence).

The nootropic effect of noopept is selective. The drug in a wide range of doses (0.1-200 mg/kg) does not exhibit either a stimulating or sedative effect, does not impair coordination of movements, does not cause a muscle relaxant effect. Long-term use of noopept at a dose of 10 mg/kg does not lead to a change in the spectrum of its neurotropic activity, no cumulative effect, development of tolerance and the appearance of new components of the drug's action were noted. When the drug was discontinued, minor activation phenomena were observed, without signs of the development of "rebound" anxiety, characteristic of some nootropics. For clinical use, a dose of noopept of 20 mg/day is recommended.

The presence of a wide range of nootropic and neuroprotective activity in noopept was established in patients with memory, attention and other intellectual-mnestic functions disorders after TBI and in chronic cerebrovascular insufficiency. When taking noopept, compared to piracetam, the frequency of side effects of therapy decreases (12% and 62%, respectively). The effectiveness and good tolerability of noopept allow us to recommend it as a drug of choice in the treatment of neurotic disorders.