Russian Classification of Nootropics

Despite quite a long history of nootropic drugs there is still no single classification which would be ok with both pharmacologists and clinical physicians. On the one hand, this is because of the extreme diversity of the group and the difference of the action of its constituent substances, and on the other, vagueness of the nootropic effect itself. That is why researchers have to deal with classification approaches which are not always best to fit the purpose. In this article several Russian classifications of nootropics are suggested in order to help you structure their wide variety.

Classification of Nootropics #1   

One of the first and most complete Soviet classifications of nootropics proceeded from the chemical structure, as well as the mechanism of the cellular action of substances. It included 8 main groups of drugs: 

  1. Derivatives of pyrrolidone: piracetam, etiracetam, pramistar (pramiracetam) and others.
  2. Derivatives of dimethylaminoethanol: dimethylaminoethanol (DMAE), meclofenoxate, euclidan and others.
  3. Derivatives of pyridoxine: pyritinol, gutimine.
  4. Derivatives of GABA: nicotinoyl GABA (Picamilon), phenibut, pantogam, gammalon, sodium oxybutyrate and others.
  5. Cerebrovascular substances: vinpocetine, nicergoline (Sermion), hydergine and others.
  6. Neuropeptides and their analogues: ACTH and its fragments (Semax), vasopressin and oxytocin, thyroliberin and melanostatin, endogenous opioids, pyroglutamyl, dipeptides.
  7. Antioxidants: 2-ethyl-6-methyl-3-hydroxypyridine (Mexidol), ionol.
  8. Various substances with a component of nootropic action: aethimizolum, orotic acid, oxymetacil, xanthinol nicotinate, ginseng and others. 

Later, this classification of nootropics was modified and supplemented with an emphasis not on the chemical structure, but on the pharmacological properties of substances. 

Classification of Nootropics #2

In the updated form this classification of nootropics consists of two large groups: nootropics with a predominance of the mnestic effect (“cognitive enhancers“) and substances of a mixed type (“neuroprotectors“). Each of them is represented by several subgroups: 

I. Nootropic drugs with a dominant mnestic effect 

1. Pyrrolidone nootropics (racetams), mainly of metabolic action: piracetam, oxiracetam, aniracetam, pramistar (pramiracetam), rolziracetam and others.

2. Cholinergic substances: 

  • increased synthesis of acetylcholine and its release (choline chloride, phosphatidylserine, Lecithin, L-carnitine, aminopyridine derivatives and others), 
  • cholinergic receptor agonists (oxotremorine, bethanechol, spiropyridines, dinucleotides and others), 
  • acetyl cholinesterase inhibitors: physostigmine, tacrine, amiridine, galantamine, metrifonate, velnacrine and others, 
  • substances with a mixed mechanism: demanol aceglumate (DMAE), nerve growth factor (NGF), sulbutiamine and others.

3. Neuropeptides and their analogs: ACTH and its fragments (Semax), somatostatin, oxytocin and its analogs, thyroliberin and its analogs, neuropeptide Y, substance P, cholecystokinin-8 (CCK), peptide analogs of piracetam, prolyl endopeptidase inhibitors.

4. Substances with an effect on the excitatory amino acid system: glutamic acid, memantine, milacemide, glycine, nooglutyl. 

II. Mixed nootropic drugs with a wide range of effects (“neuroprotective agents”) 

1. Brain metabolism activators: L-carnitine, phosphatidylserine, homopantothenic acid esters, xanthine derivatives of pentoxyphylline, propentophylline, tetrahydroquinones, etc.

2. Cerebral vasodilators: vinpocetine, nicergoline, etc.

3. Calcium antagonists: nimodipine, cinnarizine, flunarizine, etc. 

4. Antioxidants: Mexidol, dibunol, exiphon, pyritinol, tirilazad mesylate, meclofenoxate, atherovit (alpha-tocopherol), etc.

5. Substances affecting the GABA system: Picamilon, phenibut, pantogam, gammalon, nicotinamide, phenotropil, sodium oxybutyrate, neurobutal, etc.

6. Substances from different groups: aethimizolum, orotic acid, oxymetacil, beglimin, naftidrofuryl, cerebrocrast, ginseng, rhodiola rosea, etc. 

It is clear that this classification is much more complete than the previous one and includes many new substances. Though this form has a larger pharmacological orientation, it nevertheless turns out to be quite cumbersome, partly due to the inclusion of a number of little-known and sometimes clinically insufficiently approved compounds.

Classification of Nootropics #3

In order to simplify the task and bring the classification of nootropics closer to the needs of practical medicine, another option is recommended, which is based on the direction of the pharmacological effect. In a modified form, such a classification may include 4 main groups of drugs: 

  1. Substances with a pronounced psycho-energizing component, effective for mental retardation in children, trauma, alcoholism, ischemia: piracetam, encephabol.
  2. Substances with a relatively high nootropic effect for the treatment of amnesia and effective in neurodegenerative diseases of the central nervous system (senile dementia, Alzheimer’s disease): centrophenoxine, pramistar (pramiracetam), aniracetam, choline and Lecithin.
  3. Cerebroprotectors, which have a predominant effect on cerebral blood flow and which are used for disorders of cerebral circulation: vinpocetine, Picamilon, nicergoline.
  4. Substances of auxiliary action directly involved in the metabolism of nerve cells: orotic and nicotinic acids. 

However, even this principle of dividing nootropics cannot be considered satisfactory. Here we are faced with another problem – an excessive limitation of the range of nootropic drugs and not a very successful attempt to consolidate certain clinical indications for strictly defined substances. 

Classification of Nootropics #4

Taking into account the problems outlined, another classification of nootropics was suggested by prof. Edward Arushanian (M.D.). It might not coincide with what biohackers in the West think about nootropics and cognitive enhancers but it is what neurology and pharmacology students find in their text-books. This version is less simplified than the previous one, but at the same time, is not too cumbersome: 

1) Derivatives of pyrrolidone or racetams: piracetam, oxiracetam, aniracetam, pramistar (pramiracetam) et al. It is a group with the most pronounced universal properties (stabilization of cell membranes, vasoactive, antioxidant, synaptotropic and other effects).

2)    Synaptotropic drugs:

a) Cholinomimetic agents: anticholinesterase compounds (physostigmine, rivastigmine, tacrine, amiridine, donepezil) and mediator precursors (choline, citicoline).

b) GABAergic substances: aminalon, pantogam, picamilon, phenibut, sodium oxybate.

c) Glutamatergic drugs: glutamic acid, selective stimulants of the glycine site (glycine), blockers of NMDA receptors (dizocilpine, memantale).

d)    Dopamine agonists: levodopa, midantan.

3)  Neuroprotective agents: calcium channel blockers (nimodipine, cinnarizine), antioxidants (mexidol, meclofenoxate), membrane stabilizers (phosphatidylserine, L-carnitine), Ginkgo biloba preparations (Tanakan).

4)  Cerebral vasodilators: vinpocetine, nicergoline (Sermion), pentoxyphyllinum, xantinol nicotinate.

5)  Neuropeptides, hormones and hormone-like drugs: Cerebrolysin, a stimulant for the synthesis of neurotrophins idebenone, vasopressin and its analogs, dipeptide analogs of piracetam (Noopept), ACTH4-10 drugs (Semax), thyroliberin and its derivatives, thyroid hormones (thyroxin, triiodothyronine), ovarian hormones (estrogens), pineal gland hormone melatonin. 

6)  Group of nootropic-like drugs that facilitate cognitive activity along with some basic specific effects. This can include many types of psychotropic compounds: 

  • herbal adaptogens (ginseng, leuzea, rhodiola rosea),
  • psychomotor stimulants (caffeine),
  • benzodiazepine anxiolytics,
  • representatives of various antidepressants,
  • stimulants of peripheral, in particular, retinal receptors (such as strychnine),
  • platelet aggregation inhibitors,
  • anti-inflammatory agents,
  • vitamin complexes.

The proposed classification of nootropic drugs also has its drawbacks. In particular, it was not possible to build it entirely on a functional basis. It must be assumed that in the future there will be new nootropic drugs, which are in dire need for modern clinical practice. Hence the classification of substances will be subject to further changes.

About the Author of the latest Classification of Nootropics

Dr Arushanian the author of the russian classification of nootropics photo
Dr. Edward Arushanian – the author of the Russian classification of Nootropics

Edward Arushanian is the Doctor of Medicine, professor and the current Head of the Pharmacology faculty of the Stavropol State Medical University (Russia) and an acting member of the New York Academy of Sciences (since 1995). Dr. Arushanian was granted the Honored Scientist of Russia in 1995 as well as a number of other academic Soviet and Russian awards. His professional interest lies within neuropharmacology and neurophysiology. Dr. Arushanian is the author of 855 scientific papers including 27 monographs and about 150 foreign articles, some of them can be found in PubMed. He was the mentor of 9 doctoral theses. 

Dr. Edward Arushanian was born in 1934 in Vladivostok (Russia) and started his scientific path at the age of 19 in the Pavlov university in Saint-Petersburg. In his younger years Edward Arushanian worked under the mentorship of Dr. Vladimir Zakusov, one of the most prominent medical academicians of the USSR who was the Head of the Zakusov Institute of Pharmacology where Semax, Selank, Noopept and many other medications were discovered. 

Dr Arushanian the author of the russian classification of nootropics during his 3rd year of university
Edward Arushanian during his 3rd year of university (1954)

After graduating with honors from the Pavlov university Edward Arushanian started his scientific career in a position of medical assistant at the Chita State Academy of Medicine (Chita, Russia) where he rose to the Head of the faculty of Pharmacology. In 1964 Dr. Arushanian organized a micro-neurophysiological laboratory which was the first in Siberia at that time. Over 13 years of work in Chita Dr. Arushanian developed a strong scientific and professoriate team, his faculty carried out research devoted to the study of physiological and pharmacological features of the basal ganglia of telencephalon with assistance of colleagues from cross-disciplinary faculties: psychiatrist, neuropathologist, etc. which resulted in the development of the concept of the antipsychotic effect of neuroleptics, and new methods of treating parkinsonism and epilepsy. The materials were presented in international congresses in San-Francisco (1972), Helsinki (1975), and Paris (1978) at the IV International Congress of Pharmacologists where Dr. Arushanian was the main speaker. 

Dr. Arushanian the author of the Russian classification of nootropics

In 1983 Dr. Arushanian left his high post in Chita university at the summit of his fame and regard, and moved to the city of Stavropol to look after his elderly parents. There he was assigned Head of the Pharmacology faculty of the Stavropol State Medical University. He had to start it all over and re-create the faculty: the team, the equipment, the research. Under the leadership of professor Arushanian, the department launched a set of works to elaborate the unified scientific program “Chronopharmacology”. The task of the research team was to study the dependence of the pharmacological effect on the state of biological rhythms and the effect of drugs on the oscillatory processes in the body. 

For the first time the hypothesis of the chronopharmacological effect of antidepressants was substantiated in experimental conditions. A new point of view on the origin of the anti-anxiety action of anxiolytic drugs was suggested. Chronobiological characteristics of the action of psychomotor stimulants like caffeine and amphetamines was presented. A whole group of papers was devoted to elucidating the contribution of the visual analyzer to the psychostimulant effect, and the possibility of direct pharmacological intervention in the function of the photosensitive apparatus of the retina was postulated. The obtained results were included in a complex of works published after 2000.

Dr. Arushanian described his relations with science in the following manner: “Since my student years Science has become one of the most exciting pursuits of my life. There is always a place for discovery if you avoid the tick-box approach. A creative insight may lead to big conclusions that give you joy, equal with the joy of creativity in art. This is what prompts me to do Science outside the box.

Dr. Arushanian is a man of many interests. Apart from science he is a passionate stamp and rock collector. Recently he has also started collecting butterflies. According to E. Arushanian collectors are people who know how to look at the world with wide-open eyes and make their life interesting in any circumstances.

The staff of the Pharmacology faculty of the Stavropol State Medical University (2012)

Dr. Arushanian has respect towards young students. His willingness to listen attentively and delve into any assumptions go hand in hand with high demands, without any discounts for youth or inexperience. Everyone is given the right to think and work on their own, but everyone must bear full responsibility for their own actions. 

K. S. Elbekyan, Doctor of Biology, Head of the Department of General and Biological Chemistry of the Stavropol State Medical University, Professor

His lectures raise students’ interest due to their unusual construction, clear logical structure, and excellent literary language. Before we never had lecturers who could talk so smoothly and easily about such complex things as pharmacology which is by no means an easy subject. When I had to make the choice of a specialization, I gave preference to pharmacology without any hesitation, largely thanks to the personality of Dr. Arushanian.

K.B. Ovanesov, Doctor of Medical Sciences, Professor of the Department of Pharmacology of the Stavropol State Medical University

I have known Dr. Arushanian for thirty years, and what fascinates me most about this man is that he never stops at what has been achieved. It is impossible to catch up with him, he is always ahead. 

A.V. Popov, Doctor of Medical Sciences, Professor of the Department of Pharmacology of the Stavropol State Medical University

I have not been within the walls of my alma mater for over 20 years, and the first question I asked, once setting my foot here again, was about the Professor. I was immensely glad that my dear Teacher, to whom I owe everything – my interest in science, my successful professional career, my understanding of life – not only continues to work, being the country’s leading specialist in the field of chronobiology, but he looks even younger, and more full of spirits than I remember him. It was important for me to feel his support, and paternal guidance during my student years. I felt it even when I moved abroad. I continued and developed his scientific ideas on the other side of the earth. 

Orhiy Paul Botvev, professor at the University of Texas (USA), graduate of the Stavropol State Medical University

Dr Arushanian the author of the russian classification of nootropics at the grant contest among medical students
Dr. Arushanian at the grant contest among medical students in Stavropol, 2013

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