Story behind Meldonium Mildronate

In this article you will be able to learn how Meldonium was invented, what it uses are , what it  originally was meant to do. You will find out about people behind it and about the events that led to Meldonium Mildronate as we know it now. And all this is told by the man who has been known as Meldonium's inventor - Ivars Kalvins.

Meldonium's story has been full of controversy, serious allegations and interesting events. Most of the world became to know Meldonium after the bright tennis star Maria Sharapova tested  positive to then recently banned doping substance Meldonium. To others , especially those who have lived in Eastern Europe it has been a well known drug . In fact in those countries Meldonium often is considered to be more like a vitamin not a drug. After Sharapova's ban there have been many others who have tested positive for this alleged doping agent – professional boxer Alexander Povetkin, olympic athlete in curling Alexander Krushelnitsky and many others. The research has been vague and not decisive regarding its effect as doping agent, but still it remains banned.

How Meldonium was invented?

Ivars Kalvins tells that scientific discoveries often are accidental. Although the original task for the time was very typical – vast majority of Soviet scientific work was military contracts. At the time  USSR air defense missiles used fuel which relatively quickly went bad, had to be changed and destroyed . The task of destroying the toxic product was difficult and dangerous. So the military tasked Ivars Kalvins and his coworkers with figuring out how to turn this military toxic surplus material into a useful material.

You have to also understand that the surplus was measurable in hundreds of thousands of tonnes so in theory the task was not only to think of a clever way to recycle the toxic rocket fuel but recycle in such a way that this vast amount would be used up. Only few industries can use such a huge amount of material. Ivars Klavins and his team came up with a clever idea to convert the fuel which chemically is called Dimethylhydrazine to amino acid or cyclic amino acid and create substance to use in agriculture.

In the laboratory, when they were researching possible molecules that could regulate the growth of plants or livestock, they found that these substances already have a similar molecule in nature, except that one carbon atom must be replaced by a nitrogen atom.This would then be called '' hydrazinium betaine'' , a class of compounds that did not exist before. They named the molecule GBB and found that in nature it converts to vitamin BT (L-carnitine), the so-called growth vitamin.

They had a new, stable substance which, incidentally, is less toxic than sugar or salt. Its semi-toxic dose in mice was found to be two grams per kilogram of  weight. Eating that much sugar would kill a person... Then the tests on plants and animals began. The results were particularly good with animals living under stress. Livestock kept in semi-starvation and cramped conditions were not uncommon in those days. This led to the development of quaterine, which can be used in livestock and veterinary medicine. This name was given so that there would be no confusion, because in human medicine this substance is used with a much higher degree of purification, which is why it is called Mildronate .

When the story of Mildronate began?

The task was given in the mid 70s. By the early 1980s, extensive trials were under way and mildronate was approved for medical use in 1984. At the beginning Klavins team received only 20 000 roubles from the state budget for this project. For reference modest monthlt salary in Soviet Russia in 1980s was 80-100 rubbles.  The Institute's core funding was relatively large and they were able to carry out the basic work on their own resources, even without sufficiently extensive clinical experiments. But they had their own experimental plant, which nowadays is manufatcuring plant of large pharmaceutical company Grindeks, so they were able to successfully and quickly start manufacturing the product by themselves. After much thought and research about the potential of the new molecule - Meldonium , they concluded that it could optimise the use of oxygen in the body, helping to use it more economically by correcting metabolic processes It meant that it can be used to treat a wide range of diseases - atherosclerosis, thrombus formation, heart attack, myocardial infarction, heart failure. At first, this caused puzzlement and confusion among doctors, which has not been completely overcome even now. But clinical trials have shown that mildronate has a very wide range of uses in cardiovascular and other diseases.

What is the most interesting use of Mildronate?

I.Klavins considers  that one of the most interesting uses is that Mildronate can even get rid of hangovers. Even more, if a person knows that he or she will inevitably have to drink alcohol in the evening and does not want to become an alcoholic, four capsules of Mildronate will help to keep him or her awake and to avoid complications the next day, as it will prevents oxygen starvation in the brain. For the same reason Mildronate is useful to prevent physical and emotional overstrain, it also improves sugar metabolism in diabetes.

As the cell optimises energy production under conditions of oxygen deprivation and its utilisation by the body improves, performance increases. That is why in the Soviet times, the military was one of the first to take an interest in the substance - it was given to airplane pilots, submarine crews.

What about Mildronate in sports?

Ivars Klavins states that Mildonate in 1980s was used without any disguise, because Mildronate is not a doping, but optimises metabolism. One thing is clear: just taking Mildronate will not achieve anything.  With Mildronate, you can raise that overtraining threshold higher, preventing the dangerous consequences of overtraining - heart failure. However, with any preparation, this should be done under the supervision of qualified trainers and sports doctors who can assess the situation and thus help to improve results.

In the former USSR and post-socialist countries, Mildronate is widely used in sport.Ivars Klavins states that  they have even received official letters of thanks from the Zalgiris basketball team when it beat the Americans in Seoul, from the Russian ski team after the Calgary Olympics. The athletes said that the preparation helps them to feel better after intense training because Mildronate is not energy itself, but it helps to optimize energy production and usage. However, the body will alw ays resist external influences and adapt to drugs. That is why Klavins recommends taking Mildronate in courses not all the time.

What would be the most common use of Mildronate?

Because mildronate improves mental and work ability, I recommend that students take mildronate ten days before the start of exams - for people of normal physique up to one gram ( 2 x 500mg capsules) a day, but maybe only for a month and a half. Mildronate could also be used before surgery and during the recovery period, as these processes are also associated with oxygen starvation. Likewise, any mental or emotional overload requires energy - the brain can eat 40 percent of the energy. Others say that sugar is a white death, but if the brain of an individual who has and intelectual load does not receive sugar, a rather dangerous situation can arise.

Who created Mildronate?

The preparation was synthesized by my own colleague Valentīna Semeņihina, who is also still working at the institute. However, it took the intensive and creative work of many people for the substance to become a medicine. Together with technology developers, pharmaceutical, analytical, standardization research, the team of authors consisted of about 30 people. There was another good opportunity in USSR times. We were able to work with any research institute in Soviet Russia. It was interesting for the partners, because they received a pharmacologically really active substance free of charge, they could work with it, carry out interesting research. We, in turn, received their results free of charge.

What is the working principle of Mildronate?

It is based on an original mechanism of action that combines restriction of fatty acid flux across cell membranes, prevention of activated fatty acid accumulation, restoration of ATP transport, acceleration of glucose oxidation, optimisation of cellular oxygen utilisation, etc., which together protect the heart and other organs and tissues against overload and oxygen starvation.