Innovative molecule will become the base of antidepressant of new generation

Clinical depression, or major depressive disorder is not only a fashionable name for depressed mood, but a complex of severe symptoms. Patients with such diagnosis are not able to feel joy, suffer from guilt feeling, asthenia, apathy and fatigue, their cognitive functions and memory become worse, they experience trouble sleeping and problems with appetite. Such condition can last for months, and in bad cases – for years, that leads to the loss of job and suicidal thoughts. It’s practically impossible to cope with it without proper medical help – combination of drugs and psychotherapy. Russian scientists from The Federal Research Centre “Fundamentals of Biotechnology” of the Russian Academy of Sciences (Research Center of Biotechnology RAS) tested a new potential antidepressant on rodents. Revolutionary approach to treatment of depression and and related cognitive dysfunction connected with it is described in a scientific article, published in one of the most authoritative magazines in the field of neuropsychopharmacology – ACS Chemical Neuroscience, in which only 6 articles of Russian authors have been published within the period of its existence and not an only one in the last 3 years.

According to the World Health Organization 5% adults in the world suffer from clinical depression. There are many drugs that help to fight with this disorder, but they help not every person. It happens so that patients have to try 2-3 drugs in order to find a suitable one for themselves, and often they can’t find it at all. Moreover, antidepressants have also rare but dangerous side effects. Drugs from serotonin reuptake inhibitor class can cause serotonin syndrome and disturb the rhythm of the heart, while monoamine-oxidase inhibitors don’t go with drugs that are used for treatment of elevated blood pressure, and if you take them together with food that contains tyramine (ripe cheese, chocolate, smoked meat) it can lead to hypertonic crisis. That is why it is important to continue the search for new antidepressive drugs for realization of individual approach to each patient. One of the potential antidepressants with new mechanism with effect on animals was studied by scientists from Laboratory of Biomedical Chemistry of The Federal Research Centre “Fundamentals of Biotechnology” of the Russian Academy of Sciences.

«ACS Chemical Neuroscience, where our article was published, is one of the most famous and authoritative magazines in the field of psychopharmacology. It was not easy to achieve this: the article was estimated by five independent reviewers and our answers on their questions were printed on 48 pages», – told about his work the doctor of pharmaceutical sciences Vadim Makarov, the head of the Laboratory of Biomedical Chemistry of The Federal Research Centre “Fundamentals of Biotechnology” of the Russian Academy of Sciences.

18 months ago laboratory of Vadim Makarov won a grant of Ministry of Education and Science of the Russian Federation for opening of youth laboratories. In The Federal Research Centre “Fundamentals of Biotechnology” of the Russian Academy of Sciences there was organized a specialized youth laboratory of medical chemistry of psychoactive drugs and there also the research work that is dedicated to elaboration of new candidate for antidepressants on the base of vindeburnol. Vindeburnol itself is a synthetic derivate of alkaloids of group of eburnamine-vincamin, known for their diverse pharmacological properties. The same active agent scientists test also on models of other diseases of central nervous system, including Alzheimer and disseminated sclerosis. The research is held together with Serbsky National Medical Research Center for Psychiatry and Narcology. The industrial partner of the project is group of companies “P-Pharm”, that gives organizing and financial support – with its help scientists carry out a search of effective derivates of eburnamine and also plan the elaboration of scaling method of full synthesis of the best molecule and testing it on animal models.

The main active ingredient of the prototype drug (vindeburnol) is able to affect neurotransmitter systems as well as the viability of nerve cells, which makes it possible to use this compound to treat various diseases that are associated with neuronal death and memory problems. The new drug can be used to treat a wide range of diseases, which is achieved through a unique mechanism of tyrosine hydroxylase activation in the Locus coeruleus of the brainstem, which causes regulation of the synthesis of many neurotransmitters and the formation of new interneuron connections.

For the research biologists used specially elaborated model of depression that have rats and mice. Rodents were influenced for a long time (21 days) by ultrasound, that provoked a depressed state. At the same time scientists made them the insertion of vindeburnol. Then they estimated effects of treatment with the help of this compound using specialized behavioral tests for depressive symptoms that rodents may have. Researchers estimated anhedonia, the central peculiarity of depression, that is expressed in inability to feel pleasure, made tests that measure the consumption of sucrose, social interaction and also despair in the test of forced swimming and other parameters. It turned out that treatment with the help of vindeburnol lowered symptoms of depression that mice and rats had.

Rodents began to drink sugared water again, to interact longer and show interest to their conspecifics, and moved more actively in the water container trying to get out of it, trying to exit from it.

Under the influence of the drug test animals had changes also on the biochemical level. In the brainstem – ancient section, that controls breathing, digestion, swallowing, heart work and other vital processes in organism – levels of neuromediators of noradrenaline, dopamine and its metabolites increased.

Organisms of rodents experienced the raise of dopamine, 3-methoxytyramine and 3,4-dihydroxyphenylacetic acid in striatum. This anatomic structure of brain helps to form conditional reflexes, influence the work of skeletal muscles, complex motional reaction and search of food. Nevertheless, target and the precise mechanism of vindeburnol action are still unknown and are the subjects of further scientific investigation.

“We are convinced that vindeburnol is a unique compound on the base of which it is possible to create drugs with antidepressive effect and new, original mechanism of work. The work of known antidepressants generally is based on the influence on the level of basic neuromediators -serotonin,  noradrenaline and dopamine. The compound that we elaborate can revolutionize the approach to treatment of depression and related cognitive dysfunction. We will continue our work and hope to bring this drug to clinical investigation in order to give patients with depression a new hope”, – concluded Vadim Makarov.