Phenotropil chemical formula. FST - Functional strength training: Phenotropil
Phenotropil is one of the most effective nootropic drugs. This is a relatively new nootropic drug from the family of piracetam derivatives, which is a modification of the original drug Piracetam. The difference between phenylpiracetam and piracetam is that its activity is 30-60 times higher, it has neuroprotective properties and increases physical performance. For all these reasons, phenylpiracetam is increasingly becoming the drug of choice among nootropics.
Phenylpiracetam ((RS)-2-(2-oxo-4-phenylpyrrolidin-1-yl)-acetamide), also known as Carphedon or Phenotropil, was developed in Russia in 1983. It was created as a nootropic and also as a means to increase physical endurance. Phenylpiracetam was synthesized from Piracetam by adding a phenyl group to the substance. Phenylpiracetam has long been popular in Russia and the post-CIS, and only recently has it become popular in the West. Its effects are described as increasing concentration, as well as improving memory and learning. There is stimulation and improvement of locomotor activity, which increases physical performance. For this reason, phenylpiracetam has been included in the list of prohibited drugs by many sports organizations, including the Olympic Committee.
The structure of phenylpiracetam is piracetam with a phenyl group attached to it. This feature significantly increases its bioavailability and increases its effectiveness by 30-60 times compared to piracetam. The addition of a phenyl group affects these properties in two ways:
High efficiency and more pronounced effects are achieved due to the ability of the molecule to more easily penetrate the blood-brain barrier.
The stimulant effects are more pronounced due to its similarity to phenylethylamines such as Adderall. Compared to other piracetams, phenylpiracetam is quite effective and has high bioavailability even when taken orally. Its half-life in humans is 3-5 hours.
Why Phenotropil was discontinued
It turns out that since April 2017, Valenta Pharm has stopped producing the nootropic drug Phenotropil.
This is due to the fact that one of the copyright holders of patents and trademarks for Phenotropil, inventor Valentina Akhapkina, stopped working with Valenta due to the fact that the company was not improving the drug. Now the copyright holders will develop this brand themselves. According to Akhapkina, the need for the drug will now be provided by the Vira Innfarm company.
Valentina Akhapkina explained to Vademecum what this decision was related to: “The drug was not introduced into pediatric practice, new dosage forms were not developed and introduced. The company’s management was only satisfied with the operation of the product, but not with its development.”
Valenta Pharm has been producing Phenotropil for more than 15 years. The annual sales volume of Phenotropil in 2016 amounted to 1 billion rubles (1.4 million packages). “According to the consulting company DSM Group, in January–October 2017, the total sales volume of Phenotropil amounted to 966.4 million rubles (1.2 million packages).
Efficiency. How is it better than piracetam?
There is a sufficient number of studies proving that phenylpiracetam, like other piracetam drugs, is effective in slowing the progression and manifestation of symptoms of cognitive impairment. In some of these studies, piracetam was used for more than one month, and its beneficial effects were due only to its effect on organic causes of cognitive impairment (dementia and stroke), rather than on traumatic brain injury.
There is only one rat study that has shown improvements in cognitive performance in relatively healthy rats, and that study only describes the effectiveness of the R-isomer (the racemic mixture, which is most commonly found in the market, did not have this effect). A cognitive enhancing effect of phenylpiracetam in young individuals cannot be excluded. Presumably, this is different from the psychostimulant effect (which is observed equally with the mentioned racemic mixture and the R-isomer). The R-isomer appears to be more active than the S-isomer when phenylpiracetam is used for conventional purposes (psychostimulation and learning enhancement), while the racemic mixture (the most commonly sold) is effective for enhancing cognitive performance, but it is unknown whether Does it have a nootropic effect in adolescents?
Dosage
Recommended dosage: 100-250 mg. Recommendations: Phenylpiracetam is soluble in water. Do not use during pregnancy or breastfeeding. Side effects - very rarely allergic reactions. Before use, consult a specialist.
Phenylpiracetam has 100% bioavailability when taken orally and is rapidly absorbed through the gastrointestinal tract and other organs. After entering the bloodstream, it easily penetrates the blood-brain barrier. 60% of the drug is excreted in the urine, the rest through the bile ducts. Metabolism occurs with the formation of 3-hydroxycarphedon and 4-hydroxycarphedon. Phenylpiracetam begins to act 1 hour after administration, its half-life is 3-5 hours.
Phenylpiracetam has neuromodulator properties. It has significant effects on the cholinergic and glutamatergic systems. It binds to acetylcholine and glutamate receptors. Phenylpiracetam also increases dopamine and norepinephrine levels in the brain, which may explain its stimulant and mood-elevating effects.
As little is known about the direct mechanism of action of phenylpiracetam as about other piracetams. It is known to increase the density of NDMA glutamate receptors in the hippocampus. It is believed that phenylpiracetam is also capable of stimulating nicotinic cholinergic receptors in the cerebral cortex and D3-dopamine receptors in the striatum.
The ability of phenylpiracetam to influence physical performance has been noted. Although phenylpiracetam has a stimulating effect, no direct effect on the cardiovascular and respiratory systems has been found. It was noted that phenylpiracetam is able to reduce the pain threshold, as well as the ability to adapt to stress. Phenylpiracetam is thought to help modulate locomotor activity in the brain.
Side effects of phenotropil
Phenylpiracetam has the same side effects and risks as most other piracetams. These include: headache, nausea, irritability and gastrointestinal problems. Due to the stimulating effect of the drug, insomnia may occur. This side effect can be avoided by reducing the dosage of the drug or adjusting the timing of its administration, since it has a fairly short half-life.
Over time, phenylpiracetam is addictive, which develops faster than other piracetams. The drug is not believed to cause addiction, but there is evidence of dependence. In general, this drug is not recommended for daily use, since with prolonged use it loses its nootropic properties. Phenylpiracetam is rarely addictive and can be considered relatively safe when used correctly.
There are no reports of deaths or severe cases when phenylpiracetam interacts with other drugs. There have been no cases of phenylpiracetam overdose. It can be considered safe when consumed in recommended dosages. You should not exceed the recommended dosage, and you should consult a specialist before taking it. Hypersensitivity to the drug may develop, so use should be started with small doses.
Like other piracetams, phenylpiracetam rarely causes side effects when used in recommended dosages. If you have a headache, you may want to increase your choline intake, which is often recommended when taking piracetam medications.
Legal status
The use of carphedon as a doping agent was first reported in 1997 and has been banned by the IOC since 1998.
The description is valid on 31.03.2014
- Latin name: Phenotropil
- ATX code: N06BX
- Active ingredient: N-carbamoylmethyl-4-phenyl-2-pyrrolidone
- Manufacturer: Valenta Pharmaceuticals, JSC, Shchelkovo, Russian Federation
Compound
One tablet contains the active substance (phenotropil) - 100 mg; excipients: potato starch - 46.48 mg; lactose monohydrate (milk sugar) - 51.52 mg; calcium stearate - 2 mg.
Release form
The tablets appear to be flat-cylindrical in shape, creamy, white or yellowish in color. Packs of 30 and 10 pieces.
Pharmacological action
What is Phenotropil ( INN - Phenotropil)? This nootropic , having a pronounced antiamnestic effect. Preparation improves memory and the learning process. Strengthens the ability to concentrate and remember. Reduces the toxic effect of certain drugs and hypnotic effects ethanol And hexobarbital . Improves mood, reduces the threshold of pain sensitivity. Increases physical performance.
Pharmacodynamics and pharmacokinetics
Once in the gastrointestinal tract, it is absorbed quickly and well. The maximum possible concentration in blood plasma can be observed after 1 hour, excreted after 3-5 hours unchanged in urine (40%), bile and sweat (60%). Not in the body .
Improves blood supply to the brain, activates and normalizes redox reactions occurring in it. In ischemic areas of the brain, it stimulates the normalization of regional blood flow. Blood supply to the lower extremities also improves.
Without affecting spontaneous bioelectrical activity of the brain and at GABA content level, increases the level, norepinephrine And . In this regard, mood and overall well-being improves.
Shows anorectic activity with long-term use. The drug in some way improves vision.
Is not carcinogen and does not have embryostatic action.
Begins to act after the first use. The critical lethal dose is 800 mg.
Indications for use of Phenotropil
What are Phenotropil tablets for?
- various diseases of the central nervous system, especially those associated with impaired blood supply to the brain or metabolic processes;
- impaired attention, memory impairment;
- some types ( And , as a side effect of the disease);
- increased psychological and physiological stress;
- indications for the use of the drug are considered to vary in severity;
- normalization of biorhythms;
- with alimentary-constitutional genesis.
Contraindications
Individual intolerance to the components of the drug. Particular caution should be used in children, patients arterial hypertension , with organic damage to the kidneys and liver, severe, and having suffered various acute psychopathic conditions.
Side effects
The most common side effect is, mainly when taking the drug 6-8 hours before bedtime.
An increase in blood pressure, psychomotor agitation, and sudden flushes of heat may be observed.
Instructions for use of Fenoptropil (Method and dosage)
Before using the drug, consult your doctor, he will advise the required dosage and duration of treatment. There is also a universal instruction for Phenotropil.
How to take the pills? Inside, orally. The medicine is drunk immediately after meals, washed down with plenty of water. Better in the morning. The maximum permissible daily dose is 750 mg. On average, it is permissible to take 100-250 mg, and 200-300 mg per day, once. If a single dose is more than 100 mg, the medicine is divided into 2 doses.
For obesity– 100-200 mg taken once in the morning, for 1-2 months.
For increased performance– 100-200 mg in the morning, for 15 days.
The average duration of treatment is about a month (up to three). If necessary, the course can be repeated for another 30 days.
Overdose
Adverse reactions may increase. To date, no cases of overdose have been reported. Treatment: depending on symptoms.
Interaction
Phenotropil enhances the effect of drugs that affect central nervous system, various antidepressants and other nootropic drugs.
Terms of sale. Phenotropil - prescription or not?
The drug is dispensed from pharmacies according to a prescription. Although there are known cases, sometimes the medicine could be purchased without a prescription.
Storage conditions
Best before date
Subject to storage conditions - 5 years.
Analogues and substitutes
Level 4 ATX code matches:
The drug has no structural analogues containing the same active ingredient. However, there is a class nootropics having similar medicinal properties. The most common analogues of Phenotropil are ( nootropil ).
What is better Phenotropil or Nootropil?
Contains another active ingredient - piracetam. The drug must be taken in courses and improvements usually occur after two weeks, unlike Phenotropil, which acts immediately.
However, when taking nootropil, it is often observed hyperstimulation of the central nervous system , due to the dissociation of the manifestation of some psychotropic effects with long-term use. Its use is justified when it is necessary to quickly mobilize the body's strength under special extreme conditions.
The price of the analogue is undoubtedly less, but the course of the drug is longer.
Alcohol and medicine Phenotropil
Due to the fact that the drug reduces the toxic effect ethanol and promotes the restoration of the central nervous system, the medicine is not just compatible with alcohol. It is used in the treatment alcoholism .
Phenotropil for weight loss
When taking the medicine, there is a decrease and increase in motor activity. In this regard, Phenotropil can be used as a drug for weight loss. It is enough to take 100-200 mg in the morning, after meals for one or two months.
Special instructions
Phenotropil is often used in sports. Drug included World Anti-Doping Agency on the list of prohibited doping .
Some compare the effect of Phenotropil with a well-known drug amphetamine , although this is not true. Most likely, the confusion is caused by the prefix “ hair dryer” (derivative ) in the title. And if the correct dosage is observed, the drug is not addictive and withdrawal syndrome .
Nootropic drug
Release form, composition and packaging
Pills from white to white with a yellowish or creamy tint, flat-cylindrical.
Excipients: lactose monohydrate - 80.5 mg, potato starch - 18 mg, calcium stearate - 1.5 mg.
10 pcs. - contour cellular packaging (1) - cardboard packs.
10 pcs. - contour cell packaging (3) - cardboard packs.
Indications
- diseases of the central nervous system of various origins, especially diseases of vascular origin or associated with metabolic disorders in the brain and intoxication (in particular, in post-traumatic conditions and phenomena of chronic cerebrovascular insufficiency), accompanied by deterioration of intellectual and mnestic functions, decreased motor activity;
- neurotic conditions, manifested by lethargy, increased exhaustion, decreased psychomotor activity, impaired attention, memory impairment;
— violations of learning processes;
— correction of the functional state of the body in extreme conditions of professional activity in order to prevent the development of fatigue and increase mental and physical performance;
— correction of daily biorhythm, regulation of the sleep-wake cycle;
— chronic (to reduce symptoms of asthenia, depression, intellectual and mental disorders).
Contraindications
- hypersensitivity to the components of the drug.
WITH caution the drug should be prescribed to patients with severe organic damage to the liver and kidneys, severe course, and severe atherosclerosis; patients who have previously suffered panic attacks, acute psychotic states, accompanied by psychomotor agitation (as there may be an exacerbation of anxiety, panic, hallucinations and delusions); patients prone to allergic reactions to nootropic drugs of the pyrrolidone group.
Dosage
The dosage regimen is set individually.
Phenotropil is taken orally immediately after meals.
The average single dose is 100-200 mg, the average daily dose is 200-300 mg. The maximum daily dose is 750 mg. It is recommended to divide the daily dose into 2 doses. A daily dose of up to 100 mg should be taken 1 time/day in the morning; a daily dose of more than 100 mg should be divided into 2 doses. The duration of treatment can vary from 2 weeks to 3 months. The average duration of treatment is 30 days. If necessary, the course can be repeated after a month.
For improving performance Prescribe 100-200 mg 1 time/day in the morning for 2 weeks (for athletes - 3 days).
At nutritional-constitutional obesity- 100-200 mg 1 time/day in the morning for 30-60 days.
Side effects
From the side of the central nervous system:(when taking the drug after 15 hours).
In some patients, in the first 3 days of use, psychomotor agitation, skin hyperemia, a feeling of warmth, and increased blood pressure occur.
Overdose
Currently, no cases of overdose of the drug Phenotropil have been reported. If necessary, carry out symptomatic therapy.
Drug interactions
Phenotropil may enhance the effect of drugs that stimulate the central nervous system, antidepressants and nootropic drugs.
Special instructions
It should be taken into account that with excessive psycho-emotional exhaustion against the background of chronic stress and fatigue, chronic insomnia, a single dose of Phenotropil on the first day can cause a sharp need for sleep. For such outpatient patients, it is recommended to start taking the drug on non-working days.
Use in pediatrics
Experimental results
Phenotropil is characterized by low toxicity, the lethal dose in an acute experiment is 800 mg/kg. Does not have a carcinogenic effect.
Instructions for medical use of the drug
PHENOTROPIL®
Trade name of the drug
FENOTROPIL®
International nonproprietary name
Dosage form
Tablets 100 mg
One tablet contains
active substance - phenotropil (N-carbamoylmethyl-4-phenyl-2-pyrrolidone) 100 mg,
excipients: lactose monohydrate, potato starch, calcium stearate
Description
Flat-cylindrical tablets from white to white with a yellowish or creamy tint
Pharmacotherapeutic group
Other psychostimulants and nootropics
PBX code N06BX
Pharmacological properties
Pharmacokinetics
Phenotropil® is quickly absorbed, penetrates various organs and tissues, and easily passes through the blood-brain barrier. The absolute bioavailability of the drug when taken orally is 100%. The maximum concentration in the blood is reached after 1 hour, the half-life is 3-5 hours. Phenotropil® is not metabolized in the body and is excreted unchanged from the body. Approximately 40% of the drug is excreted in the urine, 60% of the drug is excreted in bile and sweat. Pharmacodynamics
Phenotropil® is a nootropic drug that has
anti-amnesic effect, has a direct activating effect on the integrative activity of the brain, increases the speed of information transfer between the hemispheres of the brain, increases the resistance of brain tissue to hypoxia and toxic effects, has anticonvulsant effects and anxiolytic activity, regulates the processes of activation and inhibition of the central nervous system (CNS), improves mood.
Phenotropil® has a positive effect on metabolic processes and blood circulation in the brain, stimulates redox processes, increases the body's energy potential due to the utilization of glucose, improves regional blood flow in ischemic areas of the brain. Increases the content of norepinephrine, dopamine and serotonin in the brain, does not affect the level of gamma-aminobutyric acid (GABA) ), does not bind to either GABAA or GABAB receptors, and does not have a noticeable effect on the spontaneous bioelectrical activity of the brain.
Phenotropil® has no effect on respiration and the cardiovascular system, exhibits an unpronounced diuretic effect, and has anorexigenic activity when used in a course.
The stimulating effect of Phenotropil® is manifested in its ability to have a moderately pronounced effect on motor reactions, in increasing physical performance, in pronounced antagonism to the cataleptic effect of neuroleptics, as well as in weakening the severity of the hypnotic effect of ethanol and hexenal.
The psychostimulating effect of Phenotropil® predominates in the visionary (mental) sphere. The moderate psychostimulating effect of the drug is combined with anxiolytic activity, improves mood, and has some analgesic effect, increasing the threshold of pain sensitivity.
The adaptogenic effect of Phenotropil® manifests itself in increasing the body's resistance to stress under conditions of excessive mental and physical stress, fatigue, hypokinesia and immobilization, and low temperatures.
While taking Phenotropil®, an improvement in vision was noted, which manifests itself in an increase in acuity, brightness and visual fields.
Phenotropil® improves blood supply to the lower extremities.
With a course of use of Phenotropil®, drug dependence, tolerance, or “withdrawal syndrome” do not develop.
The effect of Phenotropil® manifests itself with a single dose, which is important when using the drug in extreme conditions.
Phenotropil® does not have teratogenic, mutagenic, carcinogenic or embryotoxic properties. Toxicity is low, the lethal dose in an acute experiment is 800 mg/kg.
Indications for use
Diseases of the central nervous system of various origins, especially those associated with vascular diseases and metabolic disorders in the brain, intoxication (in particular in post-traumatic conditions and chronic cerebrovascular insufficiency), accompanied by deterioration of intellectual and mnestic functions, decreased motor activity
Neurotic conditions manifested by lethargy, increased exhaustion, decreased psychomotor activity, impaired attention, memory impairment
Disturbances in learning processes
Mild to moderate depression
Psychoorganic syndromes manifested by intellectual-mnestic disorders and apathetic-abulic phenomena, as well as flaccid apathetic states in schizophrenia
Convulsive syndrome
Obesity (alimentary-constitutional origin)
Prevention of hypoxia, increasing resistance to stress, correction of the functional state of the body in extreme conditions of professional activity in order to prevent the development of fatigue and increase mental and physical performance, correction of the circadian rhythm, inversion of the sleep-wake cycle
Chronic alcoholism (in order to reduce the phenomena of asthenia, depression, intellectual and mental disorders).
Directions for use and doses
Phenotropil® is used orally; its intake does not depend on diet. Doses vary depending on the characteristics of the patient's condition. The average single dose is 150 mg (from 100 mg to 250 mg); the average daily dose is 250 mg (from 200 mg to 300 mg). The maximum daily dose is 750 mg. A daily dose of up to 100 mg is recommended to be taken once in the morning, and over 100 mg - divided into two doses. The duration of treatment can vary from 2 weeks to 3 months. The average duration of treatment is 30 days. If necessary, the course can be repeated after 1 month.
To increase performance - 100-200 mg once in the morning for 2 weeks (for athletes 3 days).
Side effects
Insomnia (if the drug is taken after 15:00)
Psychomotor agitation
Hyperemia of the skin, feeling of warmth
Increased blood pressure
Contraindications
Hypersensitivity to phenotropil or other components of the drug
Children and adolescents up to 14 years of age (due to the lack of clinical trial results)
Pregnancy and lactation
Drug interactions
Phenotropil® may enhance the effect of drugs that stimulate the central nervous system, antidepressants and nootropic drugs.
Special instructions
Phenotropil® is used with caution in patients with severe organic damage to the liver and kidneys, severe arterial hypertension, in patients with atherosclerosis, as well as in patients who have previously suffered panic attacks, acute psychotic states occurring with psychomotor agitation - due to the possibility of exacerbation of anxiety, panic, hallucinations and delusions, as well as in patients prone to allergic reactions to nootropics of the pyrrolidone group.
With excessive psycho-emotional exhaustion against the background of chronic stress and fatigue, chronic insomnia, a single dose of Phenotropil® in the first day can cause a sharp need for sleep. Such patients on an outpatient basis should be advised to start a course of taking the drug on non-working days.
Features of the effect of the drug on the ability to drive vehicles and potentially dangerous mechanisms
Phenotropil® does not have a sedative effect, does not reduce the speed of the psychomotor reaction and can be used in people of various professions, including those requiring increased attention and coordination of movements. However, when taking Phenotropil® against the background of chronic stress and fatigue, chronic insomnia, care should be taken when driving and working with potentially dangerous mechanisms.
Overdose
Symptoms: increased side effects.
Treatment: symptomatic therapy.
Release form and packaging
Tablets 100 mg
10 tablets each in a blister pack made of polyvinyl chloride film and printed varnished aluminum foil.
Neuromodulatory concept - a discovery by Russian scientists
Interview with Deputy General Director for Science, Director
Department of Experimental and Clinical Pharmacology of the Holding "
Domestic medicines", author of the neuromodulatory concept, developer
neuromodulator-type drugs [by the creator] –
Valentina Ivanovna Akhapkina.
Corr.: The achievements of Russian scientists in the field of pharmacology often come down to either reproducing what was created abroad, or to creating drugs from already known groups. Lately, you are increasingly hearing about some new neuromodulator drugs, for example, phenotropil, which supposedly work wonders, and what is most surprising, they say that these drugs were first developed in Russia, and the neuromodulator concept was discovered and formulated by you on the basis the results of our own long-term research. Is this so and what are the prospects for this new direction?
V.I.: God works miracles, and we are only a weak and very unsuccessful imitation of him. The creation of a new class of drugs is indeed far from an ordinary event in medicine. A specific case is a special source of pride. A lot of things came together here, and the intellect won a triumphant victory.
The very concept of “neuromodulation” in the context is modeling (from the Latin modulus - measure, sample), the model has been known to psychiatrists and cardiologists for quite a long time, and in recent years it has found application in urology. In this process, under the influence of an electric current of a certain frequency, the activity of any individual disturbed functional system of the body changes, i.e. with the help of electric current, the restoration of a sample of healthy function is simulated by encouraging the pathological, sick person to work in the required rhythm. There is some incorrectness in using the term and it would be more correct to talk not about neuromodulation, but about electromediation or neuromodeling, but the term has already come into use in a distorted form and has taken root. In our discovery we are talking about modulation (from the Latin modulatio - dimension, dimension), that is, about the proportional influence of a certain chemical substance, and not an electric current, on the functional state of the central nervous system as a whole, and the selectivity of the activity of such substances is manifested already in the very the body, depending on the presence of certain diseases and disorders or the presence of prerequisites for them. The range of medical disciplines for the use of such substances is practically unlimited, since nothing in the body occurs without the participation of the nervous system. Neuromodulators also activate the immune system. It should be noted that they both increase the activity of the nervous and immune systems at their reduced level, and reduce their activity if it is excessive.
They change, if necessary, the intra- and intersystem structural relationships of various functions, structuring them. That is why the effects of these drugs are practically not felt by healthy people and are clearly manifested in patients or in situations of tension and fatigue in healthy people. The therapeutic and preventive value of such substances is still unparalleled. It is very important that such drugs are not metabolized, that is, they do not disintegrate and do not bind to other substances in the body of humans and animals, and are completely eliminated from the body unchanged, that is, the “Moor” has done his job and... gets out. Efficiency begins to develop from the very first use of such substances.
This discovery and creation of a new class of drugs - neuromodulators - will not be appreciated immediately, as usual. I know that some foreign companies and scientists are already trying to take this personally and even assign authorship to themselves, but I first filed an application for the invention and then announced it publicly, so the priority in this case is ours, Russia. I was surprised and pleased that when I first publicly announced this discovery and invention in April 2006, expecting resistance from my colleagues, scientists unanimously supported me. How my country and the people in it have changed in recent years! We can afford to openly rejoice in the achievements of our colleagues. Here is the first miracle of the transformation of consciousness to the original source. It may seem strange to you, but the latter pleased me much more than the discovery and creation of a new class of drugs itself. With the discovery of the neuromodulatory concept, practitioners received a tool for understanding the rational use and dosage of such drugs, understanding the mechanisms of their polyvalent and sometimes, at first glance, paradoxical action.
Let me note with full responsibility that this is a completely new direction in pharmacotherapy and pharmacoprophylaxis, which opens up completely new approaches and will form new views in the section of ensuring the quality of life of a modern person, and the drug phenotropil you mentioned is only the first “swallow” and the founder of a new a class of highly effective substances called neuromodulators. Believe me, it was not easy for me to maintain development in the country, to prevent the leakage of information and materials in the second half of the 80s and 90s of the last century. I don’t even want to remember those, to put it mildly, difficulties.
Corr.: But Phenotropil was originally declared by you as a nootropic drug. What has changed over the years and why did he become the founder of a new class? Tell the story of its creation.
V.I.: Initially, it was announced according to a closed plan, as a psychostimulant, then as a nootropic, and only in 2006 – as a neuromodulator. This happens until science accumulates a sufficient amount of reliable information, and who in the Soviet years would have given me the opportunity to publish my works and publicly express my opinion. The secrecy stamp was removed from it when I realized that secrets in our country at that time were resold abroad much more easily than open inventions. The end of the 80s and the dashing 90s were indeed just another hard time. Everything was falling apart. Cynicism has reached its peak. Some smart guys demanded that I hand over research materials on the drug to the Americans, then to the Italians, or to someone else. It was necessary to have not just courage, but inexhaustible willpower in order to withstand all attacks, persecution, and threats. The drug was saved for Russia due to the fact that only I had the research materials, and no one needed the husk that others made.
Back in my student years, and then at the department of the Medical Academy and then at the Institute of Medical and Biological Problems, I was engaged in science, trying to correct the state of the central nervous system with the help of various substances, and the greatest interest of these substances aroused my greatest interest in cyclic derivatives of gamma-aminobutyric acid ( GABA), a universal neurotransmitter of the brain. Collaboration with space medicine began already during my work at the department. Many scientists both here and in the rest of the world have plowed this field. Our scientists at that time were forcibly and completely devoid of any ambition, especially commercial ones, and could only afford breadth of thinking in the laboratory. Everything new was crushed by the army of scientific inquisitors at the root, even when, unable to resist their methods of influence, the scientist gave priority to the invention or discovery to them, and he himself could be completely thrown out of the authors and forgotten. There are countless examples like this. Then, having reported within the framework of socialist competition in the list of scientific works of the inquisitor, everything ordered to live long. That is why the USSR did not make mass discoveries and inventions, although in many ways it was our scientists who were the first. For example, I still don’t know of a tranquilizer that is more effective than phenazepam. In the development of psychostimulants of the sidnoimine group, we also had priority. Now it’s hard to believe, but in the Soviet Union, authors received a one-time payment of 20 rubles for an invention. With this money you could then buy seven kilograms, six hundred and ninety-two grams of doctor’s sausage at the price of two rubles and sixty kopecks per kilogram, or travel on the subway four hundred times. The authors had no rights.
The state appropriated the invention for itself, and you also had to knock on doors, proving to the state and begging it in the person of its officials that your invention was useful and necessary for the state and the people. At the same time, you were reproached every day for doing the devil and living like a parasite, since you do not create material values: you do not sow, you do not plow, you do not stand at a metalworking machine, you are not a worker or a collective farmer. From year to year, weekly on Mondays at operational meetings, I was publicly “flogged” for being passionate about science and lagging behind in socialist competition, for avoiding social activities. Things got to the point where I was forbidden to go to work at the experimental base or write anything. The typewriter, paper, pens and pencils were removed from my desk in the administrative building, everything was cleaned from both the desk and the desk’s bedside table. I had to sit on a chair at an empty table every day from nine in the morning until six in the evening and do nothing. Everyone was forbidden to talk to me. The party group leader was instructed to monitor me all this time and demonstratively wipe the dust from my table several times a day. She performed the duties assigned to her obediently and conscientiously. Exactly at nine in the morning, over the intercom, in a stern voice, the big boss asked if I had come to work, and at exactly six in the evening, if I had left, since only at six o’clock and one minute did I have the right to leave the administrative building. I played this game for two days, and on the third I left to work in the laboratory, deciding that I should let them fire me. They didn't fire me. Then, it’s true, they came up with new and new executions with the requirement to be more modest, but apparently the rumors reached the academician, because he suddenly persistently and more often than usual began to take an interest in my affairs. I invariably answered that everything was fine, he squinted his eyes slyly and said: well, well, but they told me the opposite. Then one of my high-ranking relatives visited our Institute on a working visit and they generally left me alone for a while. For some reason, the chairman of the party committee, although I was not a party member, reproached me for not informing anyone about the presence of such a relative, and the relative reproached and tried to get information from me: what was happening to me and whether everything was okay with me. I never complained to anyone and never asked anyone for anything, and I never let anyone in on my problems and affairs. To be honest, it didn't even occur to me. I was generally lucky, I worked at the forefront of my homeland, our elders, the founders of space medicine, treated me with great attention and care, and my tormentors did not have the power to clean out my brain like my desk. True, they managed to steal my dissertation along with all the drafts and destroy my career as a Soviet scientist, but that was the least of my worries. We were then “ahead of the rest” in the field of ballet and in space. We dreamed of flying to Mars and diligently prepared the Mars program. Despite everything, I managed to create a group of like-minded people from truly outstanding scientists, who never betrayed me over these many years and helped me in any way they could. I was happy. We are friends and support each other to this day.
In the 80s of the twentieth century, the nootropic concept became, as they would now say, a new hit in medicine from UCB (Belgium). It was a successful PR move. No significant scientific evidence has yet been provided for the viability of this flashy and well-organized commercial enterprise. Nevertheless, at that time it was a new word in pharmacology, which became widespread and comprehensively studied in the USSR. I am sure that if it were not for the research of Soviet scientists and not the Soviet consumer market, then piracetam would have long ago lost its relevance as a medicine, retaining itself only as a scientific example of comparison. Much earlier than piracetam, phenibut was developed in the USSR, but its developers failed to “break through” a new class of drugs, although everyone understood and clearly saw that phenibut is not a tranquilizer. Apparently, their peace and some kind of well-being were more valuable to them than the truth, and this is also their right. Everyone chooses their own path and builds their own destiny. In terms of nootropic activity, phenibut is more effective than piracetam and, unlike piracetam, has a complex of very useful properties. I also made a temporary compromise so as not to completely ruin my life’s work and it was easier for me to declare phenotropil as a nootropic, especially since it still has no equal in terms of nootropic activity. I certainly would not have been able to create a new class of drugs then. What saved me from this act was my own pedantry and meticulousness in collecting scientific evidence to formulate a new concept.
But even the presence of big names in the co-authors and the origin of phenotropil from the space industry did not help. I was ready to put anyone as a co-author just to achieve its industrial implementation. Once the director of our Institute, Academician Oleg Georgievich Gazenko, invited me to his place and said with bitterness, throwing up his hands helplessly: the drug will not work and I am powerless here, forget about the drug, this is the way it should be, I was ordered to forget and I am no longer your helper here. I didn’t bother to find out who needed it, and everything was clear. This clarity made me angry. I needed a drug of this level primarily for manned space flights and it was for this purpose that it was developed, since in world pharmacology there was no substance with the necessary activity to achieve certain goals and the required level of safety. I received a clear example of unfair competition in socialist competition with the inclusion of the administrative resource of the system. Where can we go further if such an influential figure as our academician was powerless. It was not difficult to figure out the enemy. Phenotropil was a competitor in terms of psychostimulating activity to sydnocarb, behind which stood the indisputable figure of a master in pharmacy, the author of the only reference book of medicines in the Soviet country. Moreover, not just a competitor, but a deadly competitor in comparison with psychostimulating activity and the level of safety of use. Anticipating the possibility of confrontation, I deliberately did not include in the materials the results of a comparative study of phenotropil with sydnocarb, and I did the right thing, because, as it turned out later, this was precisely what made it possible to resolve the situation to save phenotropil. I decided for myself that I would not give up, and the academician understood this in my opinion. So I had to become a warrior. My weapons were an understanding of the significance of development, a genetic lack of a sense of careerism, combined with an inflexible character, coupled with diplomacy, supported by a good upbringing. If we were talking about some ordinary development, then of course I would not waste time and energy on the fight, but the world pharmacology had nothing like it, it was a real breakthrough. Studies on dogs simulating a “disruption of higher nervous activity,” when the animal irreversibly “goes crazy” and there is no drug in the world that would prevent the development of tragic events…. There was no phenotropil before the birth! This was the final point in my conviction that I was right.
During my first visit to the Pharmacological Committee, the curator then quite openly and cynically told me: the drug will not work! Forget about the drug! The dossiers with materials were archived. When a drug is archived, no one and nothing can resurrect it.
Everyone dissuaded me from this struggle, starting from Academician O.G. Gazenko and ending with his comrades, but it was impossible to stop me. After a conversation with the chairman of the Pharmaceutical Committee, the dossier was taken out of the archive. I met another smart person along the way. There was a situation when the Pharmaceutical Committee had already authorized and approved the conduct of clinical trials at the presidium, and they immediately informed me about this by phone with congratulations, but literally 15 minutes later they called back and disappointed me again: the master arrived at the end of the meeting and canceled everything. I could no longer avoid a direct conversation with the master. Over and over again they tried to dissuade me from calling him and said that he wouldn’t accept me, that he didn’t even want to hear my last name, that when it comes to Phenotropil and me, he becomes so irritated and furious that it’s better for me not to see this and don't hear.
To the credit of the master, it must be said that he was the smartest man and apparently was intrigued by the rebellion of a fly against an elephant. I called him and he immediately, without any preamble, scheduled an audience with me, I didn’t even have time to say anything. After a personal meeting and a rather lengthy conversation, without hesitation, in my presence, he demonstrated his power to me by calling the chairman of the Pharmaceutical Committee and literally saying the following: I’m talking here with an amazing creature, not unknown to you, send phenotropil to the clinic. Soon the fairy tale is told, but not soon the deed is done. This meeting was preceded by four years of grueling struggle with experts of various stripes and directions, carrying out orders and at the same time sympathizing with me. Before going to bow to the titan, I had to ensure that all the false conclusions of the Pharmaceutical Committee experts were rewritten into objective ones. An almost impossible task, but without this it would be useless to talk to him. Detective stories were strung like beads on a thread. This was probably the first time in the USSR when the developer demanded an independent examination by specialists who were not members of the Pharmacological Committee of the USSR Ministry of Health. Oddly enough, it worked. I was lucky, the materials were sent to independent experts in St. Petersburg or what was then Leningrad. I could not imagine that this story is already widely discussed by the scientific community and is being closely followed by many. The sending of materials for independent examination was arranged by the Pharmaceutical Committee in the strictest secrecy, but the world, as you know, is not without kind and decent people, and one late evening a long-distance call rang out in my apartment. They called from St. Petersburg. The person who called introduced himself and said that he had been appointed chairman of an independent expert commission on my case. The conversation was very short. He asked me what I wanted, what conclusion. I replied that I was only interested in truth and objectivity, I didn’t need anything else. He laughed and said: well, it’s simple, we are proud of you here, don’t give up, there really is something to fight for.
Perhaps for the first time, a single group of substances was created whose activity is proven not by direct, but by indirect pharmacological effects and their combination. Although I, as a young scientist at that time, was somewhat influenced by the nootropic concept, even then I was not satisfied with much of it, and the technique of transcallosal potentials, in my understanding, was a road to nowhere.
The more animal and human research data accumulated, the more doubts I had about nootropics. I tried to combine them, the adaptogenic effect identified in them, and the topic of my dissertation was devoted to this. However, the application of the adaptogenic concept is good for fundamental science and practically healthy individuals, but as soon as we begin to interpret it on a sick organism, then everything falls apart. We, doctors, cannot afford to fail, recognizing that the process of treatment and recovery is a process of adaptation of the body to the disease and its subsequent coexistence with the disease. The relationship between the body and the source of the disease is a fierce struggle, and this struggle is brilliantly described by the great scientist of the twentieth century, G. Selye, whom I respect. The organism sometimes loses, but a viable organism wins this war, it must win. This is predetermined by nature through natural selection. The strongest survive, the weak perish. We, humanity, “played a joke” on ourselves here too, by eradicating natural selection of ourselves and this is no longer reversible, and this ultimately led to the need for a massive expansion of the search for various drugs for our salvation. We are no longer destined to recognize the norms of biological health obtained through natural selection and we are unlikely to survive without drugs. Of course, here you can talk for a long time about the primacy of the egg or the chicken, but these arguments are scholastic and not productive. We have what we have and build on what we have. Otherwise, science will not develop.
I set myself the task of creating a substance that would be able to open up the body’s reserves without depleting them and would be a universal key to this secret door, both for opening it and closing it at the right moment. I understood that this substance either must itself be double and consist of biologically active and mirror-image antipodal molecules, or the radicals of the substance molecule themselves must have their own radicals that are spatially independent of each other, allowing the molecule to change its spatial orientation in the biological environment and, as it were, adapt to the environment with any changes, have both lipophilic and hydrophilic properties, and in the external environment such a substance or its combination must be inert. It seems that we managed to get both, and the third, at once.
Compared to other Institutes, we had unique capabilities for research involving human subjects. The further I went, the more I understood the shortcomings of the nootropic concept as it existed, but it was the existence of this concept that helped me get to the bottom of the truth, working backwards. Nootropic activity cannot be a precursor to other effects, rather the opposite, since the higher integrative functions of the brain play a huge role in adaptive reactions, but even before their evolutionary formation there was biological life of quite complex forms. In fact, any disease can disrupt memory to one degree or another, but drugs that only improve memory do not treat the disease that indirectly caused the memory disorder. True, in order to prove all this, it was necessary to obtain such a unique substance, which is now known to many under the name phenotropil.
The history of its synthesis also has its own interesting things. On our instructions, chemists synthesized many dozens of substances, including derivatives of pyrrolidone, or the cyclic form of GABA. Some of them were interesting from a clinical point of view, but did not suit me as a specialist involved in the correction of a person’s functional state in relation to the conditions of space flights of various durations, where the requirements for drugs are much higher and stricter than in ground-based medicine. It seemed like everything was tried, but the desired result could not be achieved. In 1978, during a meeting with a group of chemists, Professor Yu.I. Baukov, I asked them to try to synthesize an asymmetric substance with the inclusion of a phenyl radical at position four of the pyrrolidone ring while retaining the standard carbamoylmethyl component in the molecule. I had my own thoughts and reasoning based on knowledge of physics and electrochemistry, which I never ignored, and physics was always my favorite subject. These arguments of mine were met without enthusiasm, and arguments were given about the inconsistency of my hypothesis. Nevertheless, I managed to persuade him to fulfill my request, if only for the sake of laughter. What happened next showed the promise of unconventional thinking. At the very first studies, the resulting substance not only confused, but broke all established canons. It worked in almost all monopathological models, demonstrating diametrically opposite activity. A combination, for example, of psychostimulant and anticonvulsant or psychostimulant and anxiolytic effects. We got something that, according to all the canons, could not happen. I'm not even talking about the powerfully expressed nootropic effect, which, to be honest, interested me the least. What was needed were complex polymodels that carried not individual mono-disorders, but their maximum complex with a set of neurological and mental symptom complexes, both reduced and increased functional severity. It could happen that in case of complex complex pathologies, phenotropil would “silence” or show only one effect. Then my neuromodulatory concept would have failed using phenotropil as an example. We took two complex models of acute stroke, especially since it is known not only that nootropics are ineffective in strokes, but also that their use is contraindicated in strokes of various etiologies. The effect in experimental models of ischemic and hemorrhagic stroke exceeded expectations. There was no doubt that phenotropil is a neuromodulator, and all its other components of action, including nootropic, stem from neuromodulatory activity. Now there is no need to make excuses and mutter something incomprehensible regarding its effectiveness in the flu epidemic, the treatment of alcoholism, prostate, sexual disorders, vision, inflammatory processes, circulatory disorders not only of a central nature, but also of the periphery. This substance is of course not yet ideal, but there is no better one yet and we now know where to strive. The immunotropic properties of this drug have yet to be studied. So far, the first steps have been taken in this direction, but they are also encouraging.
I want to emphasize once again that phenotropil is not a nootropic drug or an antidepressant, a psychostimulant, anxiolytic, analgesic, antipsychotic, antihypoxic, anticonvulsant, or adaptogen. It is the first neuromodulator, which is probably the future of medicine in the near future in about fifty years. It is from its neuromodulatory activity that all its components of effectiveness stem. At the same time, it is indicated for treatment of any of the above components.
Corr.: If neuromodulators are so versatile, then wouldn’t it be worth conducting research to study their effect on the possibility of treating diseases such as HIV infection or preventing influenza in oncology?
V.I.: I can only regret the passivity of specialists in AIDS and viral diseases, who are still ignoring research on this substance in their fields. If even a negative result were obtained, then this would provide food for further understanding. It is known that in science any result is positive, since it makes it possible to advance and determine the boundaries of safety. All hope lies only in young scientists who are as persistent and fearless as we were during a very difficult period in our history. In virology, it is more difficult to study phenotropil. It is unlikely that it will be possible to obtain any results on the activity of viruses in a test tube, and these are the screening methods used there. It is difficult to overcome stereotypes. In this case, the presence of the whole organism and the study of indirect influence, if any, are necessary. As for oncology, it has already aroused interest among specialists for its use in order to increase the threshold of pain sensitivity, which sharply reduces the use of narcotic analgesics, or reduces their doses and corrects side effects, as well as to improve the quality of life. In experimental studies, this drug prevents the growth of malignant tumors and increases the life expectancy of animals with cancer, but the positive results of experimental studies on animals have more than once failed in clinical studies using other drugs as an example. This is a rare area of medicine where it is impossible to extrapolate the results a priori, even conjecturally. Special studies in the clinic are required. The neuromodulatory concept in pharmacology has only lifted the curtain on new advances.
Corr.: What is the range of use of neuromodulators and phenotropil in particular?
V.I.: The circle is wide. This is psychiatry, neurology, therapy in the broadest sense, addiction medicine, extreme medicine, etc. In this interview, I will not list specific diseases and disorders for which the effectiveness of the use of neuromodulators has already been proven using phenotropil as an example. There is special literature for this. I agreed to the interview with only one purpose, to convey first-hand to our fellow citizens the truth about some of our domestic achievements and to show by example that we should never give up and not be afraid to swim against the tide. This year marks exactly 31 years since my idea to synthesize this substance. Please note that for almost 15 years of them we had to simply survive, and for 4 years we had to fight against bureaucratic arbitrariness. So only 12 years were devoted exclusively to science in this area, but they also involved continuous overcoming of human stupidity and envy. That’s why I loved working on holidays, weekends and in the summer, when everyone was resting and no one was bothering me. That's all the arithmetic is. How many wonderful things could be done without wars of various calibers and scales.
Corr.: Valentina Ivanovna, in your opinion, will the current global financial crisis throw science back to the position of the 90s?
V.I.: There is nowhere to throw our Russian science further. It stuck to enthusiasts and still does. Academic science will, of course, begin to suffer again, since over the past five years it has gained a little footing due to government support and injections from big business, which was just beginning to acquire some contours of civilization, but with the weakening and instability of the ruble, business began to play on exchange rate differences, financial institutions busy with the same thing. For 15 years, we have not even tried to overcome the vicious circle of oil dependence and have not started creating our own industrial base in all vital industrial sectors that ensure the independence, stability and prosperity of the state. You know, when financiers and analysts begin to convince one another of the benefits of a weak ruble, their national currency, it’s not even funny. Imagine a doctor who rejoices at the growing weakness of the patient day by day due to the treatment methods of this very doctor. Introduced? Now formulate the necessary actions for a patient who comes to such a doctor.
I would really like to see my Russia proud, independent and self-sufficient. Five years of certain stability have already swept away the dollar in one fell swoop. What are we waiting for? When will the American economy start to pick up? She will start, there is no doubt about that yet, but what will happen to us? Isn't it time to use our own natural resources to develop ourselves and build our own industry? America gave us all, against our will, another chance. Will we be able to use it, will we want to? The situation is unique for Russia, if you put your head to it.
Corr.: If it’s not a secret, tell us how you got into business.
V.I.: Like everyone else, out of yet another hopelessness. I saved developments, but lately I haven’t been involved in business. Only science. I met young, energetic and hopefully decent partners - businessmen. So, having retained all my potential, I with great pleasure handed over my business to them in finished form. It will be a pity if they do not survive in the current conditions.
Corr.: But you could simply sell your developments, as many did in the dashing 90s, or leave the country with them.
V.I.: I could, but it’s not mine. My land and homeland are here. We'll all leave, so who will stay? In a fit of despair, of course, I had to think about this more than once, especially since there were many proposals, but here the pride of the Russian man reared up. Whether this is good or bad is not for me to judge, but I am who I am. I wouldn’t wish such a difficult life on anyone, but for us it’s still impossible to do otherwise. Let everyone think for themselves and choose their own path. I do not condemn the scientists who left the country and I understand them. No one would run from something good. I know that our specialists were the best. Foreigners simply would not have survived in our conditions, but our nation is already tired of surviving for a century in a row and the gene pool is catastrophically depleted. Here, even neuromodulators may be powerless against an infinite number of different “buts,” and it may turn out that most people simply cannot afford to buy them.
Corr.: Summing up our meeting, I want to ask you: was such a struggle worth even such an outstanding invention? Life, as we know, is short.
V.I.: Was there another way out? Phenotropil is only a by-product of global research into the formation of a concept regarding the correction of the biological system, although the product turned out to be unique of its kind. Science, of course, would survive without me, but without it I would no longer be me and would not be interesting even to myself. Then, it’s a colossal energy boost when you know that the result of your work literally brings practical benefits to millions of people. Phenotropil now helps to cope in some situations and where previously medicine was practically helpless or incapable. Every step forward is positive. I wouldn't be able to stagnate in one place for a long time or move backwards. I need to move forward, even if it’s in a spiral. I'm so interested in living. In addition to science, I also exceeded the entire human program: I planted a lot of trees, built a house, raised children. My life story is just another confirmation of the truth of the thesis - “the one who walks can master the road.”
The conversation was conducted by a correspondent for the magazine "Polyclinic"
Ekaterina Chursina
PS: such an interview, rare in its honesty and sincerity, is an excellent indicator of how
under the Soviet political regime, people made their achievements not THANKS to him,
and DESPITE him, and more often DESPITE him, overcoming his fierce resistance.
Naturally, the regime attributed any of their successes to itself. What the neo-Sovietists are continuing now.
